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  • Kinetics  (137)
  • American Association for the Advancement of Science (AAAS)  (137)
  • Annual Reviews
  • Nature Publishing Group
  • Periodicals Archive Online (PAO)
  • 2005-2009
  • 1990-1994  (114)
  • 1980-1984  (23)
  • 1992  (59)
  • 1990  (55)
  • 1980  (23)
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  • American Association for the Advancement of Science (AAAS)  (137)
  • Annual Reviews
  • Nature Publishing Group
  • Periodicals Archive Online (PAO)
  • Springer  (17)
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  • 2005-2009
  • 1990-1994  (114)
  • 1980-1984  (23)
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  • 1
    Publication Date: 1990-08-10
    Description: The stimulation of phospholipase A2 by thrombin and type 2 (P2)-purinergic receptor agonists in Chinese hamster ovary cells is mediated by the G protein Gi. To delineate alpha chain regulatory regions responsible for control of phospholipase A2, chimeric cDNAs were constructed in which different lengths of the alpha subunit of Gs (alpha s) were replaced with the corresponding sequence of the Gi alpha subunit (alpha i2). When a carboxyl-terminal chimera alpha s-i(38), which has the last 38 amino acids of alpha s substituted with the last 36 residues of alpha i2, was expressed in Chinese hamster ovary cells, the receptor-stimulated phospholipase A2 activity was inhibited, although the chimera could still activate adenylyl cyclase. Thus, alpha s-i(38) is an active alpha s, but also a dominant negative alpha i molecule, indicating that the last 36 amino acids of alpha i2 are a critical domain for G protein regulation of phospholipase A2 activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gupta, S K -- Diez, E -- Heasley, L E -- Osawa, S -- Johnson, G L -- DK37871/DK/NIDDK NIH HHS/ -- GM30324/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 10;249(4969):662-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2166341" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/pharmacology ; Animals ; Arachidonic Acid ; Arachidonic Acids/metabolism ; Cell Line ; Chlorides/pharmacology ; Enzyme Activation ; GTP-Binding Proteins/*genetics/metabolism ; Inositol Phosphates/metabolism ; Kinetics ; Lithium/pharmacology ; Lithium Chloride ; Macromolecular Substances ; *Mutation ; Phospholipases/*metabolism ; Phospholipases A/*metabolism ; Phospholipases A2 ; Receptors, Purinergic/drug effects/*physiology ; Restriction Mapping ; Thrombin/antagonists & inhibitors/*pharmacology ; Transfection
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  • 2
    Publication Date: 1990-08-17
    Description: The transcription factor C/EBP uses a bipartite structural motif to bind DNA. Two protein chains dimerize through a set of amphipathic alpha helices termed the leucine zipper. Highly basic polypeptide regions emerge from the zipper to form a linked set of DNA contact surfaces. In the recently proposed a "scissors grip" model, the paired set of basic regions begin DNA contact at a central point and track in opposite directions along the major groove, forming a molecular clamp around DNA. This model predicts that C/EBP must undertake significant changes in protein conformation as it binds and releases DNA. The basic region of ligand-free C/EBP is highly sensitive to protease digestion. Pronounced resistance to proteolysis occurred when C/EBP associated with its specific DNA substrate. Sequencing of discrete proteolytic fragments showed that prominent sites for proteolysis occur at two junction points predicted by the "scissors grip" model. One junction corresponds to the cleft where the basic regions emerge from the leucine zipper. The other corresponds to a localized nonhelical segment that has been hypothesized to contain an N-cap and facilitate the sharp angulation necessary for the basic region to track continuously in the major groove of DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuman, J D -- Vinson, C R -- McKnight, S L -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):771-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Research Laboratories, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2202050" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Chromatography, High Pressure Liquid ; DNA/*metabolism ; DNA-Binding Proteins/metabolism ; Kinetics ; Leucine ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Peptide Fragments/metabolism ; Peptide Hydrolases/*metabolism ; Protein Conformation ; Transcription Factors/*metabolism ; Trypsin/metabolism
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-04-06
    Description: The rate of release of guanine nucleotides from the ras proteins (Ras) is extremely slow in the presence of Mg2+. It seemed likely, therefore that a factor might exist to accelerate the release of guanosine diphosphate (GDP), and hence the exchange of GDP for guanosine triphosphate (GTP). Such a factor has now been discovered in rat brain cytosol. Brain cytosol was found to catalyze, by orders of magnitude, the release of guanine nucleotides from recombinant v-H-Ras protein bound with [alpha-32P]GDP. This effect occurred even in the presence of a large excess of Mg2+, but was destroyed by heat or by incubation of the cytosol for an hour at 37 degrees C in the absence of phosphatase inhibitors. The effect was observed with either v-H-Ras or c-H-Ras, but not with p25rab3A, a small G protein with about 30% similarity to Ras. The effect could not be mimicked by addition of recombinant Ras-GAP or purified GEF, a guanine nucleotide exchange factor involved in the regulation of eukaryotic protein synthesis. By gel filtration chromatography, the factor appears to possess a molecular size between 100,000 and 160,000 daltons. This protein (Ras-guanine nucleotide-releasing factor, or Ras-GRF) may be involved in the activation of p21ras.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfman, A -- Macara, I G -- CA 43551/CA/NCI NIH HHS/ -- ES 01247/ES/NIEHS NIH HHS/ -- GM 41220/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):67-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, University of Rochester Medical Center, NY 14642.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2181667" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding, Competitive ; Brain/metabolism ; Cholic Acids ; Cytosol/*metabolism ; Guanine Nucleotides/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate) ; Guanosine Diphosphate/*metabolism ; Guanosine Triphosphate/analogs & derivatives/metabolism ; Hot Temperature ; Immunosorbent Techniques ; Kinetics ; Magnesium Chloride/pharmacology ; Molecular Weight ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins p21(ras) ; Rats ; Thionucleotides/metabolism
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  • 4
    Publication Date: 1990-11-30
    Description: Conducting gramicidin channels form predominantly by the transmembrane association of monomers, one from each side of a lipid bilayer. In single-channel experiments in planar bilayers the two gramicidin analogs, [Val1]gramicidin A (gA) and [4,4,4-F3-Val1]gramicidin A (F3gA), form dimeric channels that are structurally equivalent and have characteristically different conductances. When these gramicidins were added asymmetrically, one to each side of a preformed bilayer, the predominant channel type was the hybrid channel, formed between two chemically dissimilar monomers. These channels formed by the association of monomers residing in each half of the membrane. These results also indicate that the hydrophobic gramicidins are surprisingly membrane impermeant, a conclusion that was confirmed in experiments in which gA was added asymmetrically and symmetrically to preformed bilayers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connell, A M -- Koeppe, R E 2nd -- Andersen, O S -- GM21342/GM/NIGMS NIH HHS/ -- GM34968/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 30;250(4985):1256-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1700867" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane Permeability ; Chemistry, Physical ; Electric Conductivity ; Gramicidin/*chemistry/metabolism ; Ion Channels/*chemistry/physiology ; Kinetics ; Lipid Bilayers/*chemistry ; Macromolecular Substances ; Molecular Sequence Data ; Physicochemical Phenomena ; Protein Conformation
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  • 5
    Publication Date: 1990-09-28
    Description: The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lupu, R -- Colomer, R -- Zugmaier, G -- Sarup, J -- Shepard, M -- Slamon, D -- Lippman, M E -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1552-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Binding, Competitive ; Breast Neoplasms ; Cell Line ; Chromatography, Affinity ; Female ; Humans ; Kinetics ; Ligands ; Molecular Weight ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/genetics/immunology/*metabolism ; Proto-Oncogenes ; Receptor, Epidermal Growth Factor/isolation & purification/*metabolism ; Transfection
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-05-04
    Description: The amino acid sequences of three fragments of cyanogen bromide-digested human placental inositol 1,2-cyclic phosphate 2-phosphohydrolase, an enzyme of the phosphatidylinositol signaling pathway, are identical to sequences within lipocortin III, a member of a family of homologous calcium- and phospholipid-binding proteins that do not have defined physiological functions. Lipocortin III has also been previously identified as placental anticoagulant protein III (PAP III) and calcimedin 35 alpha. Antibodies to PAP III detected PAP III and inositol 1,2-cyclic phosphate 2-phosphohydrolase with identical reactivity on immunoblotting. In addition, inositol 1,2-cyclic phosphate 2-phosphohydrolase was stimulated by the same acidic phospholipids that bind lipocortins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross, T S -- Tait, J F -- Majerus, P W -- HLBI 14147/HL/NHLBI NIH HHS/ -- HLBI 16634/HL/NHLBI NIH HHS/ -- HLBI 40801/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 May 4;248(4955):605-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2159184" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Annexin A3 ; Annexins ; Calcium-Binding Proteins/*genetics ; Female ; Humans ; Immunoblotting ; Kinetics ; Molecular Sequence Data ; Phosphoric Diester Hydrolases/*genetics/isolation & purification/metabolism ; Placenta/*enzymology ; Pregnancy
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  • 7
    Publication Date: 1990-09-28
    Description: Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1 alpha) of the HBGF-1 beta precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1 alpha lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imamura, T -- Engleka, K -- Zhan, X -- Tokita, Y -- Forough, R -- Roeder, D -- Jackson, A -- Maier, J A -- Hla, T -- Maciag, T -- HL 32348/HL/NHLBI NIH HHS/ -- HL 35627/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1567-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1699274" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding, Competitive ; Cattle ; Cell Division/drug effects ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; DNA Replication/drug effects ; Endothelium, Vascular/drug effects/metabolism ; Fibroblast Growth Factor 1/*genetics/metabolism/pharmacology ; Kinetics ; Mice ; Mitogens/pharmacology ; Molecular Sequence Data ; *Mutation ; Oligonucleotide Probes ; Receptors, Mitogen/metabolism ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Proteins/metabolism/pharmacology ; Transcription, Genetic/drug effects
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-29
    Description: Soluble and hydrophobic lipid breakdown products have a variety of important signaling roles in cells. Here sphingoid bases derived in cells from sphingolipid breakdown are shown to have a potent and direct effect in mediating calcium release from intracellular stores. Sphingosine must be enzymically converted within the cell to a product believed to be sphingosine-1-phosphate, which thereafter effects calcium release from a pool including the inositol 1,4,5-trisphosphate-sensitive calcium pool. The sensitivity, molecular specificity, and reversibility of the effect on calcium movements closely parallel sphingoid base-mediated inhibition of protein kinase C. Generation of sphingoid bases in cells may activate a dual signaling pathway involving regulation of calcium and protein kinase C, comparable perhaps to the phosphatidylinositol and calcium signaling pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghosh, T K -- Bian, J -- Gill, D L -- NS19304/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1653-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163543" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/pharmacology ; Animals ; Calcimycin/pharmacology ; Calcium/*metabolism ; Cell Line ; Kinetics ; Phosphoric Monoester Hydrolases/metabolism ; Phosphorylcholine/analogs & derivatives/pharmacology ; Protein Kinase C/metabolism ; Second Messenger Systems/drug effects ; Sphingosine/*analogs & derivatives/*pharmacology ; Thermodynamics
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-10-12
    Description: Voltage-dependent ion channels are responsible for electrical signaling in neurons and other cells. The main classes of voltage-dependent channels (sodium-, calcium-, and potassium-selective channels) have closely related molecular structures. For one member of this superfamily, the transiently voltage-activated Shaker H4 potassium channel, specific amino acid residues have now been identified that affect channel blockade by the small ion tetraethylammonium, as well as the conduction of ions through the pore. Furthermore, variation at one of these amino acid positions among naturally occurring potassium channels may account for most of their differences in sensitivity to tetraethylammonium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacKinnon, R -- Yellen, G -- GM 43949/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 12;250(4978):276-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218530" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Electric Conductivity ; Kinetics ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligonucleotide Probes ; Potassium Channels/drug effects/genetics/*physiology ; Tetraethylammonium ; Tetraethylammonium Compounds/*pharmacology
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  • 10
    Publication Date: 1990-02-16
    Description: Sulfonylurea-sensitive adenosine triphosphate (ATP)-regulated potassium (KATP) channels are present in brain cells and play a role in neurosecretion at nerve terminals. KATP channels in substantia nigra, a brain region that shows high sulfonylurea binding, are inactivated by high glucose concentrations and by antidiabetic sulfonylureas and are activated by ATP depletion and anoxia. KATP channel inhibition leads to activation of gamma-aminobutyric acid (GABA) release, whereas KATP channel activation leads to inhibition of GABA release. These channels may be involved in the response of the brain to hyper- and hypoglycemia (in diabetes) and ischemia or anoxia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amoroso, S -- Schmid-Antomarchi, H -- Fosset, M -- Lazdunski, M -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):852-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Pharmacologie Moleculaire et Cellulaire, UPR 411 du CNRS, Valbonne, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2305257" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*physiology ; Animals ; Cell Hypoxia ; Deoxyglucose/pharmacology ; Glucose/metabolism/*pharmacology ; Hypoglycemic Agents/*pharmacology ; In Vitro Techniques ; Kinetics ; Oligomycins/pharmacology ; Potassium/pharmacology ; Potassium Channels/drug effects/*physiology ; Rubidium/metabolism ; Structure-Activity Relationship ; Substantia Nigra/drug effects/*physiology ; gamma-Aminobutyric Acid/*metabolism
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  • 11
    Publication Date: 1990-05-04
    Description: Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the gamma isozyme of PLC (PLC-gamma) in vitro and in living cells. The role of PLC-gamma in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-gamma on cellular responses to PDGF. Overexpression of PLC-gamma correlated with PDGF-induced tyrosine phosphorylation of PLC-gamma and with PDGF-induced breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2). However, neither bradykinin- nor lysophosphatidic acid-induced phosphoinositide metabolism was enhanced in the transfected cells, suggesting that the G protein-coupled phosphoinositide responses to these ligands are mediated by other PLC isozymes. The enhanced PDGF-induced generation of inositol trisphosphate (IP3) did not enhance intracellular calcium signaling or influence PDGF-induced DNA synthesis. Thus, enzymes other than PLC-gamma may limit PDGF-induced calcium signaling and DNA synthesis. Alternatively, PDGF-induced calcium signaling and DNA synthesis may use biochemical pathways other than phosphoinositide metabolism for signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Margolis, B -- Zilberstein, A -- Franks, C -- Felder, S -- Kremer, S -- Ullrich, A -- Rhee, S G -- Skorecki, K -- Schlessinger, J -- New York, N.Y. -- Science. 1990 May 4;248(4955):607-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rorer Biotechnology, King of Prussia, PA 19406.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2333512" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/physiology ; Cattle ; Cell Division/*drug effects ; Cells, Cultured ; DNA Replication/drug effects ; Genetic Vectors ; Inositol Phosphates/metabolism ; Isoenzymes/biosynthesis/*genetics/metabolism ; Kinetics ; Mice ; Platelet-Derived Growth Factor/*pharmacology ; Second Messenger Systems/*drug effects ; Transfection ; Type C Phospholipases/biosynthesis/*genetics/metabolism
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: An antibody elicited to a distorted N-methyl porphyrin catalyzed metal ion chelation by the planar porphyrin. At fixed Zn2+ and Cu2+ concentrations, the antibody-catalyzed reaction showed saturation kinetics with respect to the substrate mesoporphyrin IX (2) and was inhibited by the hapten, N-methylmesoporphyrin IX (1). The turnover number of 80 hour-1 for antibody-catalyzed metallation of 2 with Zn2+ compares with an estimated value of 800 hour-1 for ferrochelatase. The antibody also catalyzed the insertion of Co2+ and Mn2+ into 2, but it did not catalyze the metallation of protoporphyrin IX (3) or deuteroporphyrin IX (4). The antibody has high affinity for several metalloporphyrins, suggesting an approach to developing antibody-heme catalysts for redox or electron transfer reactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cochran, A G -- Schultz, P G -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):781-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389144" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/*metabolism ; Antigens/immunology ; Catalysis ; Cobalt/metabolism ; Copper/metabolism ; Ferrochelatase/metabolism ; Kinetics ; Manganese/metabolism ; Mesoporphyrins/immunology/metabolism ; Metals/*metabolism ; Porphyrins/*metabolism ; Zinc/metabolism
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  • 13
    Publication Date: 1992-10-09
    Description: During early development of the mammalian cerebral cortex, young neurons migrate outward from the site of their final mitosis in the ventricular zone into the cortical plate, where they form the adult cortex. Time-lapse confocal microscopy was used to observe directly the dynamic behaviors of migrating cells in living slices of developing cortex. The majority of cells migrated along a radial pathway, consistent with the view that cortical neurons migrate along radial glial fibers. A fraction of cells, however, turned within the intermediate zone and migrated orthogonal to the radial fibers. This orthogonal migration may contribute to the tangential dispersion of clonally related cortical neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Rourke, N A -- Dailey, M E -- Smith, S J -- McConnell, S K -- EY06314/EY/NEI NIH HHS/ -- NS09027/NS/NINDS NIH HHS/ -- NS28587/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Oct 9;258(5080):299-302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411527" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Carbocyanines ; Cell Movement ; Cerebral Cortex/cytology/*growth & development ; Culture Techniques ; Ferrets ; Fluorescent Dyes ; Immunohistochemistry ; Kinetics ; Lasers ; Microscopy ; Neurons/*physiology ; Vimentin/immunology
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  • 14
    Publication Date: 1992-11-13
    Description: When glycine418 of Escherichia coli glutathione reductase, which is in a closely packed region of the dimer interface, is replaced with a bulky tryptophan residue, the enzyme becomes highly cooperative (Hill coefficient 1.76) for glutathione binding. The cooperativity is lost when the mutant subunit is hybridized with a wild-type subunit to create a heterodimer. The mutation appears to disrupt atomic packing at the dimer interface, which induces a change of kinetic mechanism. A single mutation in a region of the protein remote from the active site can thus act as a molecular switch to confer cooperativity on an enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scrutton, N S -- Deonarain, M P -- Berry, A -- Perham, R N -- New York, N.Y. -- Science. 1992 Nov 13;258(5085):1140-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439821" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Escherichia coli/*enzymology/genetics ; Genes, Bacterial ; Glutathione/metabolism ; Glutathione Reductase/*chemistry/genetics/metabolism ; Glycine/chemistry ; Kinetics ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; *Mutagenesis, Site-Directed ; NADP/metabolism ; Plasmids ; Protein Multimerization ; Tryptophan/chemistry
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-10
    Description: Diacylglycerols, which are generated during phospholipase-catalyzed hydrolysis of phospholipids, stimulated actin polymerization in the presence of highly purified plasma membranes from the cellular slime mold Dictyostelium discoideum. The increased rate of actin polymerization apparently resulted from de novo formation of actin nucleation sites rather than uncapping of existing filament ends, because the membranes lacked detectable endogenous actin. The increased actin nucleation was mediated by a peripheral membrane component other than protein kinase C, the classical target of diacylglycerol action. These results indicate that diacylglycerols increase actin nucleation at plasma membranes and suggest a mechanism whereby signal transduction pathways may control cytoskeletal assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shariff, A -- Luna, E J -- GM-33048/GM/NIGMS NIH HHS/ -- R01 GM033048/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):245-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology Group, Worcester Foundation for Experimental Biology, Shresbury, MA 01545.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373523" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Alkaloids/pharmacology ; Animals ; Calcium/pharmacology ; Cell Membrane/drug effects/*metabolism ; Dictyostelium/*metabolism ; Diglycerides/*pharmacology ; Kinetics ; Macromolecular Substances ; *Naphthalenes ; Polycyclic Compounds/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Staurosporine ; Tetradecanoylphorbol Acetate/pharmacology ; Time Factors
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  • 16
    Publication Date: 1992-05-01
    Description: A DNA-nicking activity was detected in the sera of patients with various autoimmune pathologies and was shown to be a property of autoantibodies. The DNA hydrolyzing activity, which was purified by affinity and high-performance liquid chromatography, corresponded in size to immunoglobulin M (IgM) and IgG and had a positive response to antibodies to human IgG. The DNA hydrolyzing autoantibodies were stable to acid shock and yielded a DNA degradation pattern that was different from that of deoxyribonuclease (DNase) I and blood DNase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuster, A M -- Gololobov, G V -- Kvashuk, O A -- Bogomolova, A E -- Smirnov, I V -- Gabibov, A G -- New York, N.Y. -- Science. 1992 May 1;256(5057):665-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉V.A. Engelhardt Institute of Molecular Biology, Academy of Sciences of Russia, Moscow.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1585181" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/pharmacology ; Acetic Acid ; Autoantibodies/isolation & purification/*metabolism ; Autoimmune Diseases/*metabolism ; Chromatography, High Pressure Liquid ; DNA/*metabolism ; DNA Polymerase I/metabolism ; Deoxyribonuclease I/metabolism ; Electrophoresis, Agar Gel ; Humans ; Immunoglobulin G/isolation & purification/metabolism ; Immunoglobulin M/isolation & purification/metabolism ; Kinetics ; Lupus Erythematosus, Systemic/immunology ; Plasmids
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  • 17
    Publication Date: 1992-05-01
    Description: A membrane polypeptide involved in K+ transport in a higher plant was cloned by complementation of a yeast mutant defective in K+ uptake with a complementary DNA library from Arabidopsis thaliana. A 2.65-kilobase complementary DNA conferred ability to grow on media with K+ concentration in the micromolar range and to absorb K+ (or 86Rb+) at rates similar to those in wild-type yeast. The predicted amino acid sequence (838 amino acids) has three domains: a channel-forming region homologous to animal K+ channels, a cyclic nucleotide-binding site, and an ankyrin-like region.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sentenac, H -- Bonneaud, N -- Minet, M -- Lacroute, F -- Salmon, J M -- Gaymard, F -- Grignon, C -- New York, N.Y. -- Science. 1992 May 1;256(5057):663-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochimie et Physiologie Vegetales, ENSA-M/INRA/CNRS URA 573, Montpellier, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1585180" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Arabidopsis Proteins ; Biological Transport ; Blotting, Southern ; Carrier Proteins/chemistry/genetics ; *Cloning, Molecular ; DNA/genetics ; Deoxyribonuclease EcoRI ; Gene Expression ; Kinetics ; Molecular Sequence Data ; Plant Proteins/chemistry/*genetics ; Plants/*genetics ; Potassium/*metabolism ; Potassium Channels/chemistry/*genetics ; Saccharomyces cerevisiae/*genetics ; Sequence Homology, Nucleic Acid
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  • 18
    Publication Date: 1992-08-14
    Description: A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ecker, D J -- Vickers, T A -- Bruice, T W -- Freier, S M -- Jenison, R D -- Manoharan, M -- Zounes, M -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):958-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ISIS Pharmaceuticals, Carlsbad, CA 92008.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1502560" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA, Viral/metabolism ; Gene Products, tat/metabolism ; HIV/*genetics ; Kinetics ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Oligoribonucleotides/*chemistry ; RNA, Viral/*chemistry/genetics/metabolism ; tat Gene Products, Human Immunodeficiency Virus
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate-binding protein (G protein) in the membranes of these cells. Activation of this G protein by somatostatin stimulated the dephosphorylation of exogenous epidermal growth factor receptor prepared from A-431 cells in vitro. This pathway may mediate the antineoplastic action of somatostatin in these cells and in human tumors and could represent a general mechanism of G protein coupling that is utilized by normal cells in the hormonal control of cell growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, M G -- Florio, T -- Stork, P J -- New York, N.Y. -- Science. 1992 May 22;256(5060):1215-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1350382" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Carcinoma, Squamous Cell ; Cell Line ; Cell Membrane/metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Diphosphate/analogs & derivatives/pharmacology ; Humans ; Kinetics ; Pancreatic Neoplasms ; Peptides/metabolism ; Pertussis Toxin ; Phosphorylation ; Protein Kinases/metabolism ; Protein Tyrosine Phosphatases/*metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Somatostatin/*pharmacology ; Thionucleotides/pharmacology ; Virulence Factors, Bordetella/pharmacology
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-10
    Description: Many specific DNA-binding proteins bind to sites with dyad symmetry, and the bound form of the protein is a dimer. For some proteins, dimers form in solution and bind to DNA. LexA repressor of Escherichia coli has been used to test an alternative binding model in which two monomers bind sequentially. This model predicts that a repressor monomer should bind with high specificity to an isolated operator half-site. Monomer binding to a half-site was observed. A second monomer bound to an intact operator far more tightly than the first monomer; this cooperativity arose from protein-protein contacts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, B -- Little, J W -- GM24178/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 10;255(5041):203-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Arizona, Tucson 85721.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553548" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*metabolism ; Base Sequence ; Binding Sites ; DNA, Bacterial/*metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonucleases ; Escherichia coli/*metabolism ; Kinetics ; Macromolecular Substances ; Models, Structural ; Molecular Sequence Data ; Oligodeoxyribonucleotides/metabolism ; Operon ; Rec A Recombinases/genetics ; Repressor Proteins/metabolism ; *Serine Endopeptidases
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-06
    Description: Trypsin (Tr) and chymotrypsin (Ch) have similar tertiary structures, yet Tr cleaves peptides at arginine and lysine residues and Ch prefers large hydrophobic residues. Although replacement of the S1 binding site of Tr with the analogous residues of Ch is sufficient to transfer Ch specificity for ester hydrolysis, specificity for amide hydrolysis is not transferred. Trypsin is converted to a Ch-like protease when the binding pocket alterations are further modified by exchange of the Ch surface loops 185 through 188 and 221 through 225 for the analogous Tr loops. These loops are not structural components of either the S1 binding site or the extended substrate binding sites. This mutant enzyme is equivalent to Ch in its catalytic rate, but its substrate binding is impaired. Like Ch, this mutant utilizes extended substrate binding to accelerate catalysis, and substrate discrimination occurs during the acylation step rather than in substrate binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hedstrom, L -- Szilagyi, L -- Rutter, W J -- DK21344/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 6;255(5049):1249-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hormone Research Institute, University of California, San Francisco 94143-0534.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546324" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chymotrypsin/*chemistry/metabolism ; Hydrolysis ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Mutagenesis, Site-Directed ; Protein Conformation ; Substrate Specificity ; Trypsin/*chemistry/genetics/metabolism
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  • 22
    Publication Date: 1992-10-16
    Description: Double-strand breaks (DSBs) in Saccharomyces cerevisiae can be repaired by gene conversions or by deletions resulting from single-strand annealing between direct repeats of homologous sequences. Although rad1 mutants are resistant to x-rays and can complete DSB-mediated mating-type switching, they could not complete recombination when the ends of the break contained approximately 60 base pairs of nonhomology. Recombination was restored when the ends of the break were made homologous to donor sequences. Additionally, the absence of RAD1 led to the frequent appearance of a previously unobserved type of recombination product. These data suggest RAD1 is required to remove nonhomologous DNA from the 3' ends of recombining DNA, a process analogous to the excision of photodimers during repair of ultraviolet-damaged DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fishman-Lobell, J -- Haber, J E -- GM01722/GM/NIGMS NIH HHS/ -- GM20056/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 16;258(5081):480-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411547" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA Repair ; DNA, Fungal/genetics ; Deoxyribonucleases, Type II Site-Specific/*metabolism ; Gene Conversion ; Kinetics ; *Recombination, Genetic ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins ; Sequence Deletion ; Ultraviolet Rays
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  • 23
    Publication Date: 1990-12-21
    Description: Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cunningham, B C -- Bass, S -- Fuh, G -- Wells, J A -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1709-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2270485" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chlorides/*pharmacology ; Growth Hormone/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligonucleotide Probes ; Plasmids ; Protein Conformation ; Receptors, Prolactin/drug effects/genetics/*metabolism ; Restriction Mapping ; Zinc/metabolism/*pharmacology ; *Zinc Compounds
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  • 24
    Publication Date: 1990-11-23
    Description: Detailed kinetic investigations of a catalytic antibody that promotes the hydrolyses of an anilide and phenyl ester show that this catalyst uses a multistep kinetic sequence resembling that found in serine proteases to hydrolyze its substrates, although antibody was elicited to a single transition-state analog. Like the serine proteases the antibody catalyzes the hydrolysis reactions through a putative covalent intermediate, but unlike the enzymes it may use hydroxide ion to cleave the intermediates. Nevertheless, the antibody is a potent catalyst with turnover at higher pH values rivaling that of chymotrypsin. This analysis also reveals that turnover by the antibody is ultimately limited by product desorption, suggesting that improvements in catalytic efficiency may be achieved by judicious changes in the structure of the substrate, so that it is not superimposable on that of the eliciting hapten.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benkovic, S J -- Adams, J A -- Borders, C L Jr -- Janda, K D -- Lerner, R A -- GM4385801/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 23;250(4984):1135-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pennsylvania State University, Department of Chemistry, University Park 16802.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2251500" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Aniline Compounds/metabolism ; Antibodies/*metabolism ; Catalysis ; Enzymes/*metabolism ; Hydrogen-Ion Concentration ; Hydrolysis ; Kinetics ; Nitrophenols/metabolism ; Spectrometry, Fluorescence ; Thermodynamics
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-05-11
    Description: Regulated expression of bacterial genes allows a pathogen to adapt to new environmental conditions within the host. The synthesis of over 30 Salmonella proteins is selectively induced during infection of macrophages. Two proteins induced by Salmonella are the heat shock proteins GroEL and DnaK. Two avirulent, macrophage-sensitive mutants of Salmonella synthesize GroEL and DnaK but fail to synthesize different subsets of proteins normally induced within the macrophage. Enhanced expression of selected Salmonella proteins contributes to bacterial survival within macrophages and may also contribute to the apparent immunodominance of heat shock proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchmeier, N A -- Heffron, F -- New York, N.Y. -- Science. 1990 May 11;248(4956):730-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1970672" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/*biosynthesis/genetics/isolation & purification ; Cell Line ; Chaperonin 60 ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; *Escherichia coli Proteins ; *HSP70 Heat-Shock Proteins ; Heat-Shock Proteins/*biosynthesis/genetics/isolation & purification ; Kinetics ; Macrophages/*microbiology ; Molecular Weight ; Salmonella/*physiology
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  • 26
    Publication Date: 1990-07-20
    Description: Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finberg, R W -- Diamond, D C -- Mitchell, D B -- Rosenstein, Y -- Soman, G -- Norman, T C -- Schreiber, S L -- Burakoff, S J -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):287-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2115689" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/*immunology ; Antiviral Agents/*pharmacology ; Benzyl Compounds/pharmacology ; Cell Line ; Genes, MHC Class II ; HIV Envelope Protein gp120/*immunology ; HIV-1/drug effects/immunology/*physiology ; Humans ; Kinetics ; T-Lymphocytes/immunology
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  • 27
    Publication Date: 1990-07-20
    Description: Epidermal growth factor (EGF) treatment of A-431 epidermoid carcinoma cells elicited a redistribution of phospholipase C-gamma 1 (PLC-gamma 1) from a predominantly cytosolic localization to membrane fractions. The temporal coincidence of this redistribution with EGF stimulation of inositol phosphate formation and EGF increased phosphorylation of PLC-gamma 1 suggests that the membrane association of PLC-gamma 1 is a significant event in second messenger transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Todderud, G -- Wahl, M I -- Rhee, S G -- Carpenter, G -- CA24071/CA/NCI NIH HHS/ -- GM07347/GM/NIGMS NIH HHS/ -- T32 AM07491/AM/NIADDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):296-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374928" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma, Squamous Cell ; Cell Line ; Cell Membrane/drug effects/enzymology ; Cytosol/enzymology ; Epidermal Growth Factor/*pharmacology ; Humans ; Isoenzymes/*metabolism ; Kinetics ; Phosphopeptides/isolation & purification ; Protein Binding ; Trypsin ; Type C Phospholipases/*metabolism
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-31
    Description: The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herrera, V L -- Ruiz-Opazo, N -- HL 01967/HL/NHLBI NIH HHS/ -- HL 18318/HL/NHLBI NIH HHS/ -- HL 39267/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1023-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA 02118.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1975705" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Membrane/enzymology ; Kidney/enzymology ; Kinetics ; Molecular Sequence Data ; *Mutation ; Polymorphism, Restriction Fragment Length ; Protein Conformation ; Rats ; Rats, Inbred Strains ; Rubidium/*metabolism ; Rubidium Radioisotopes ; Sodium-Potassium-Exchanging ATPase/*genetics/metabolism
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  • 29
    Publication Date: 1990-09-28
    Description: The proliferative potential of human diploid endothelial cells is finite, and cellular senescence in vitro is accompanied by the failure of the endothelial cell to respond to exogenous growth factors. Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-1 alpha (IL-1 alpha), a potent inhibitor of endothelial cell proliferation in vitro. In contrast, transformed human endothelial cells did not contain detectable IL-1 alpha messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1 alpha transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro. Removal of the IL-1 alpha antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential. These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1 alpha.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maier, J A -- Voulalas, P -- Roeder, D -- Maciag, T -- AG07450/AG/NIA NIH HHS/ -- HL32348/HL/NHLBI NIH HHS/ -- HL35627/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1570-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, Jerome H. Holland, Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218499" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Division ; Cell Survival ; Cells, Cultured ; Endothelium, Vascular/*cytology/physiology ; Humans ; Interleukin-1/*genetics ; Kinetics ; Molecular Sequence Data ; Oligonucleotide Probes ; RNA, Antisense/*genetics
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  • 30
    Publication Date: 1990-09-21
    Description: Calmodulin is a calcium-binding protein that participates in the transduction of calcium signals. The electric phenotypes of calmodulin mutants of Paramecium have suggested that the protein may regulate some calcium-dependent ion channels. Calcium-dependent sodium single channels in excised patches of the plasma membrane from Paramecium were identified, and their activity was shown to decrease after brief exposure to submicromolar concentrations of calcium. Channel activity was restored to these inactivated patches by adding calmodulin that was isolated from Paramecium to the cytoplasmic surface. This restoration of channel activity did not require adenosine triphosphate and therefore, probably resulted from direct binding of calmodulin, either to the sodium channel itself or to a channel regulator that was associated with the patch membrane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saimi, Y -- Ling, K Y -- GM22714/GM/NIGMS NIH HHS/ -- GM36386/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1441-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, University of Wisconsin-Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2169650" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*pharmacology ; Calmodulin/genetics/*pharmacology/physiology ; Cell Membrane/physiology ; Kinetics ; Models, Biological ; Paramecium/*physiology ; Sodium Channels/drug effects/*physiology
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-30
    Description: The generation of antibodies from a bifunctional cyclic phosphinate transition-state analog provided agents capable of efficiently catalyzing both steps of the overall conversion of a substrate containing an asparaginyl-glycyl sequence through a succinimide intermediate to the products aspartyl-glycyl and the rearranged isoaspartyl-glycyl sequence. This reaction provides a potential means in addition to amide cleavage for the deactivation of protein or peptide biological functions in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbs, R A -- Taylor, S -- Benkovic, S J -- New York, N.Y. -- Science. 1992 Oct 30;258(5083):803-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park 16802.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439788" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Catalytic/*metabolism ; Asparagine/metabolism ; Aspartic Acid/metabolism ; Chromatography, High Pressure Liquid ; Dipeptides/metabolism ; Glycine/metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Peptides/chemistry/*metabolism ; Stereoisomerism ; Succinimides/metabolism
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  • 32
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-24
    Description: A cleavage reagent directed to the active site of the Tetrahymena catalytic RNA was synthesized by derivatization of the guanosine substrate with a metal chelator. When complexed with iron(II), this reagent cleaved the RNA in five regions. Cleavage at adenosine 207, which is far from the guanosine-binding site in the primary and secondary structure, provides a constraint for the higher order folding of the RNA. This cleavage site constitutes physical evidence for a key feature of the Michel-Westhof model. Targeting a reactive entity to a specific site should be generally useful for determining proximity within folded RNA molecules or ribonucleoprotein complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, J F -- Cech, T R -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):526-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1315076" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Edetic Acid/metabolism ; Free Radicals ; Guanosine/*metabolism ; Guanosine Monophosphate/metabolism ; Iron/metabolism ; Iron Chelating Agents/metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Nucleic Acid Conformation ; Pentetic Acid/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Tetrahymena/*chemistry
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  • 33
    Publication Date: 1992-07-31
    Description: Calcium-dependent glutamate secretion was reconstituted in Xenopus oocytes by injecting the oocyte with total rat cerebellar messenger RNA (mRNA). Co-injection of total mRNA with antisense oligonucleotides to synaptophysin message decreased the expression of synaptophysin in the oocyte and reduced the calcium-dependent secretion. A similar effect on secretion was observed for oocytes injected with total mRNA together with an antibody to rat synaptophysin. These results indicate that synaptophysin is necessary for transmitter secretion and that the oocyte expression system may be useful for dissecting the molecular events associated with the secretory process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alder, J -- Lu, B -- Valtorta, F -- Greengard, P -- Poo, M M -- MH 39327/MH/NIMH NIH HHS/ -- NS 22764/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 31;257(5070):657-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1353905" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Blotting, Western ; Calcimycin/pharmacology ; Calcium/*pharmacology ; Cerebellum/chemistry ; Fluorescent Antibody Technique ; Gene Expression ; Glutamates/*secretion ; Glutamic Acid ; Kinetics ; Liver/chemistry ; Microscopy, Immunoelectron ; Molecular Sequence Data ; Oligonucleotides, Antisense/pharmacology ; Oocytes/*physiology ; RNA, Messenger/genetics ; Rats ; Synaptophysin/genetics/*physiology ; Transfection ; Xenopus
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-09-11
    Description: The regulation of microtubule sliding in flagellar axonemes was studied with the use of Chlamydomonas mutants and in vitro assays. Microtubule sliding velocities were diminished in axonemes from mutant cells missing radial spoke structures but could be restored upon reconstitution with dynein from axonemes with wild-type radial spokes. These experiments demonstrate that the radial spokes activate dynein's microtubule sliding activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, E F -- Sale, W S -- GM 08367/GM/NIGMS NIH HHS/ -- HD 20497/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 11;257(5076):1557-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1387971" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Movement ; Chlamydomonas/genetics/*physiology/ultrastructure ; Dyneins/genetics/*metabolism ; Flagella/*physiology/ultrastructure ; Kinetics ; Microscopy, Electron ; Microtubules/*physiology/ultrastructure
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  • 35
    Publication Date: 1992-04-03
    Description: Steroid-thyroid hormone receptors typically bind as dimers to DNA sequences that contain repeated elements termed half-sites. NGFI-B, an early response protein and orphan member of this receptor superfamily, binds to a DNA sequence that contains only one half-site (5'-AAAGGTCA-3'). A domain separate from the NGFI-B zinc fingers, termed the A box, was identified and is required for recognition of the two adenine-thymidine (A-T) base pairs at the 5' end of the NGFI-B DNA binding element. In addition, a domain downstream of the zinc fingers of the orphan receptor H-2 region II binding protein, termed the T box, determined binding to tandem repeats of the estrogen receptor half-site (5'-AGGTCA-3').〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, T E -- Paulsen, R E -- Padgett, K A -- Milbrandt, J -- NS01018/NS/NINDS NIH HHS/ -- P01 CA49712/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 3;256(5053):107-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1314418" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; CHO Cells ; Cell Nucleus/*physiology ; Cricetinae ; DNA/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Kinetics ; Mice ; Molecular Sequence Data ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Oligodeoxyribonucleotides/metabolism ; Polymerase Chain Reaction ; Receptors, Cell Surface/*metabolism ; Receptors, Cytoplasmic and Nuclear ; Receptors, Steroid ; Recombinant Fusion Proteins/metabolism ; Sequence Homology, Nucleic Acid ; Substrate Specificity ; Transcription Factors/genetics/*metabolism ; Transfection ; Zinc Fingers/genetics
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-11-13
    Description: Two DNA strand transfer reactions occur during retroviral reverse transcription. The mechanism of the first, minus strand strong-stop DNA, transfer has been studied in vitro with human immunodeficiency virus 1 reverse transcriptase (HIV-1 RT) and a model template-primer system derived from the HIV-1 genome. The results reveal that HIV-1 RT alone can catalyze DNA strand transfer reactions. Two kinetically distinct ribonuclease (RNase) H activities associated with HIV-1 RT are required for removal of RNA fragments annealed to the nascent DNA strand. Examination of the binding of DNA.RNA duplex and single-stranded RNA to HIV-1 RT during strand transfer supports a model where the enzyme accommodates both the acceptor RNA template and the nascent DNA strand before the transfer event is completed. The polymerase activity incorporated additional bases beyond the 5' end of the RNA template, resulting in a base misincorporation upon DNA strand transfer. Such a process occurring in vivo during retroviral homologous recombination could contribute to the hypermutability of the HIV-1 genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peliska, J A -- Benkovic, S J -- AI08275/AI/NIAID NIH HHS/ -- GM13306/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Nov 13;258(5085):1112-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park 16802.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1279806" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Catalysis ; DNA, Viral/biosynthesis/chemistry/*metabolism ; Deoxyribonucleotides ; HIV Reverse Transcriptase ; HIV-1/*enzymology/genetics ; Kinetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; RNA, Transfer/metabolism ; RNA, Viral/chemistry/metabolism ; RNA-Directed DNA Polymerase/genetics/*metabolism ; Ribonuclease H/metabolism ; Templates, Genetic
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  • 37
    Publication Date: 1992-05-29
    Description: The T cell receptor (TCR) zeta chain was attached to the TCR alpha and beta extracellular domains to induce efficient expression of alpha beta heterodimers that can recognize complexes of antigen with major histocompatibility complex (MHC) molecules. Chimeric constructs expressed in RBL-2H3 cells were efficiently transported to the cell surface uniquely as disulfide-linked heterodimers. Transfectants were activated by specific antigen-MHC complexes, which demonstrated that the expressed alpha beta was functional and that CD3 was not required for antigen-MHC binding. Constructs with thrombin cleavage sites were efficiently cleaved to soluble disulfide-linked heterodimers. Thus, attachment of TCR zeta domains and protease cleavage sites to TCR alpha and beta induces expression of demonstrably functional heterodimers that can be solubilized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engel, I -- Ottenhoff, T H -- Klausner, R D -- New York, N.Y. -- Science. 1992 May 29;256(5061):1318-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1598575" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/immunology ; Disulfides ; Flow Cytometry ; Histocompatibility Antigens/metabolism ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/genetics/isolation & purification/*metabolism ; Solubility ; Transfection
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  • 38
    Publication Date: 1992-11-06
    Description: A 9.5-kilobase plasmid of Yersinia pestis, the causative agent of plague, is required for high virulence when mice are inoculated with the bacterium by subcutaneous injection. Inactivation of the plasmid gene pla, which encodes a surface protease, increased the median lethal dose of the bacteria for mice by a millionfold. Moreover, cloned pla was sufficient to restore segregants lacking the entire pla-bearing plasmid to full virulence. Both pla+ strains injected subcutaneously and pla- mutants injected intravenously reached high titers in liver and spleen of infected mice, whereas pla- mutants injected subcutaneously failed to do so even though they establish a sustained local infection at the injection site. More inflammatory cells accumulated in lesions caused by the pla- mutants than in lesions produced by the pla+ parent. The Pla protease was shown to be a plasminogen activator with unusual kinetic properties. It can also cleave complement C3 at a specific site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sodeinde, O A -- Subrahmanyam, Y V -- Stark, K -- Quan, T -- Bao, Y -- Goguen, J D -- AI22176/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Nov 6;258(5084):1004-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439793" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Bacterial Proteins ; Colony Count, Microbial ; Escherichia coli/enzymology ; Fibrinolysin/chemistry/metabolism ; Injections, Intravenous ; Kinetics ; Liver/microbiology ; Mice ; Molecular Sequence Data ; Mutation ; Plague/microbiology ; Plasmids ; Plasminogen Activators/genetics/*physiology ; Recombinant Proteins/metabolism ; Spleen/microbiology ; Tissue Plasminogen Activator/metabolism ; Urokinase-Type Plasminogen Activator/metabolism ; Yersinia pestis/*enzymology/isolation & purification/*pathogenicity
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  • 39
    Publication Date: 1992-06-05
    Description: Several classes of ribozymes (catalytic RNA's) catalyze reactions at phosphorus centers, but apparently no reaction at a carbon center has been demonstrated. The active site of the Tetrahymena ribozyme was engineered to bind an oligonucleotide derived from the 3' end of N-formyl-methionyl-tRNA(fMet). This ribozyme catalyzes the hydrolysis of the aminoacyl ester bond to a modest extent, 5 to 15 times greater than the uncatalyzed rate. Catalysis involves binding of the oligonucleotide to the internal guide sequence of the ribozyme and requires Mg2+ and sequence elements of the catalytic core. The ability of RNA to catalyze reactions with aminoacyl esters expands the catalytic versatility of RNA and suggests that the first aminoacyl tRNA synthetase could have been an RNA molecule.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piccirilli, J A -- McConnell, T S -- Zaug, A J -- Noller, H F -- Cech, T R -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1420-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1604316" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Carboxylic Ester Hydrolases/*metabolism ; Kinetics ; Models, Structural ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligoribonucleotides ; RNA, Catalytic/genetics/*metabolism ; RNA, Transfer, Amino Acyl/metabolism ; *RNA, Transfer, Met ; Substrate Specificity ; Tetrahymena/*enzymology
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  • 40
    Publication Date: 1992-12-28
    Description: Opiate drugs have potent analgesic and addictive properties. These drugs interact with receptors that also mediate the response to endogenous opioid peptide ligands. However, the receptors for opioids have eluded definitive molecular characterization. By transient expression in COS cells and screening with an iodinated analog of the opioid peptide enkephalin, a complementary DNA clone encoding a functional delta opioid receptor has been identified. The sequence shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, C J -- Keith, D E Jr -- Morrison, H -- Magendzo, K -- Edwards, R H -- DA05010/DA/NIDA NIH HHS/ -- P50 DA005010/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 18;258(5090):1952-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of California, School of Medicine, Los Angeles 90024-1759.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1335167" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding, Competitive ; Blotting, Northern ; Blotting, Southern ; Cell Line ; Cyclic AMP/metabolism ; Diprenorphine/metabolism ; Enkephalin, D-Penicillamine (2,5)- ; Enkephalins/pharmacology ; Etorphine/pharmacology ; Gene Expression ; Humans ; Kinetics ; Models, Structural ; Molecular Sequence Data ; Naloxone/pharmacology ; Narcotics/pharmacology ; Protein Structure, Secondary ; Receptors, Opioid, delta/chemistry/*genetics/*metabolism ; Sequence Homology, Amino Acid ; Transfection ; Tumor Cells, Cultured
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  • 41
    Publication Date: 1992-04-10
    Description: Nitric oxide (NO) conveys a variety of messages between cells, including signals for vasorelaxation, neurotransmission, and cytotoxicity. In some endothelial cells and neurons, a constitutive NO synthase is activated transiently by agonists that elevate intracellular calcium concentrations and promote the binding of calmodulin. In contrast, in macrophages, NO synthase activity appears slowly after exposure of the cells to cytokines and bacterial products, is sustained, and functions independently of calcium and calmodulin. A monospecific antibody was used to clone complementary DNA that encoded two isoforms of NO synthase from immunologically activated mouse macrophages. Liquid chromatography-mass spectrometry was used to confirm most of the amino acid sequence. Macrophage NO synthase differs extensively from cerebellar NO synthase. The macrophage enzyme is immunologically induced at the transcriptional level and closely resembles the enzyme in cytokine-treated tumor cells and inflammatory neutrophils.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Q W -- Cho, H J -- Calaycay, J -- Mumford, R A -- Swiderek, K M -- Lee, T D -- Ding, A -- Troso, T -- Nathan, C -- AI30165/AI/NIAID NIH HHS/ -- CA43610/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):225-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373522" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/biosynthesis/*genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cells, Cultured ; Cloning, Molecular ; Codon ; Enzyme Induction ; Interferon-gamma/pharmacology ; Isoenzymes/biosynthesis/*genetics ; Kinetics ; Lipopolysaccharides ; Macrophages/drug effects/*enzymology ; Mammary Neoplasms, Experimental ; Mice ; Molecular Sequence Data ; Molecular Weight ; Neutrophils/drug effects/enzymology ; Nitric Oxide Synthase ; Oligodeoxyribonucleotides ; Poly A/genetics ; RNA/genetics ; RNA, Messenger ; Rats ; Sequence Homology, Nucleic Acid ; Transcription, Genetic
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: Activation of B lymphocytes by engagement of their immunoglobulin M antigen receptors results in phosphorylation of a number of proteins on tyrosine residues. One such protein is p95vav, the product of the vav proto-oncogene. Tyrosine phosphorylation of p95vav occurred within seconds of immunoglobulin M cross-linking and was independent of other events induced during stimulation of B cells, such as protein kinase C activation, guanosine triphosphate-binding protein signaling, and calcium mobilization. Moreover, engagement of antigen receptors induced the rapid (approximately 5 seconds) and transient (approximately 60 seconds) association of p95vav with a 70-kilodalton tyrosine-phosphorylated protein, Vap-1, an interaction mediated by the Src homology 2 domain of p95vav. These results suggest that the vav proto-oncogene participates in the signaling processes that mediate the antigen-induced activation of B lymphocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bustelo, X R -- Barbacid, M -- New York, N.Y. -- Science. 1992 May 22;256(5060):1196-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1375396" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/analysis ; Animals ; B-Lymphocytes/immunology/*physiology ; *Cell Cycle Proteins ; Cell Line ; Kinetics ; *Lymphocyte Activation ; Mice ; Phosphorylation ; Phosphotyrosine ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-vav ; *Proto-Oncogenes ; Tyrosine/analogs & derivatives/analysis
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  • 43
    Publication Date: 1992-04-10
    Description: Mesoderm induction and body axis determination in frog (Xenopus) embryos are thought to involve growth factor-mediated cell-cell signaling, but the signal transduction pathways are unknown. Li+, which inhibits the polyphosphoinositide (PI) cycle signal transduction pathway in many cells, also disrupts axis determination and mesoderm induction. Amounts of the PI cycle-derived second messenger, inositol 1,4,5-trisphosphate, increased during mesoderm induction in normal embryos; addition of Li+ inhibited the embryonic inositol monophosphatase and reversed this increase. Embryonic PI cycle activity thus shows characteristics that indicate it may function in mesoderm induction and axis determination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maslanski, J A -- Leshko, L -- Busa, W B -- HD22879/HD/NICHD NIH HHS/ -- HD27546/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):243-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Johns Hopkins University, Baltimore, MD 21218.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1314424" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chlorides/*pharmacology ; Choline/pharmacology ; Embryo, Nonmammalian/physiology ; Female ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol Phosphates/*metabolism ; Kinetics ; Lithium/*pharmacology ; Lithium Chloride ; Mesoderm/drug effects/*physiology ; Signal Transduction/drug effects ; Teratogens/*pharmacology ; Xenopus/*embryology
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-15
    Description: In many different spatial discrimination tasks, such as in determining the sign of the offset in a vernier stimulus, the human visual system exhibits hyperacuity by evaluating spatial relations with the precision of a fraction of a photoreceptor's diameter. It is proposed that this impressive performance depends in part on a fast learning process that uses relatively few examples and that occurs at an early processing stage in the visual pathway. This hypothesis is given support by the demonstration that it is possible to synthesize, from a small number of examples of a given task, a simple network that attains the required performance level. Psychophysical experiments agree with some of the key predictions of the model. In particular, fast stimulus-specific learning is found to take place in the human visual system, and this learning does not transfer between two slightly different hyperacuity tasks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poggio, T -- Fahle, M -- Edelman, S -- New York, N.Y. -- Science. 1992 May 15;256(5059):1018-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589770" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computer Simulation ; Humans ; Kinetics ; Learning/*physiology ; Models, Biological ; Photoreceptor Cells/physiology ; Visual Acuity/*physiology ; Visual Pathways/physiology ; Visual Perception/*physiology
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-12-11
    Description: The range of messenger action of a point source of Ca2+ or inositol 1,4,5-trisphosphate (IP3) was determined from measurements of their diffusion coefficients in a cytosolic extract from Xenopus laevis oocytes. The diffusion coefficient (D) of [3H]IP3 injected into an extract was 283 microns 2/s. D for Ca2+ increased from 13 to 65 microns 2/s when the free calcium concentration was raised from about 90 nM to 1 microM. The slow diffusion of Ca2+ in the physiologic concentration range results from its binding to slowly mobile or immobile buffers. The calculated effective ranges of free Ca2+ before it is buffered, buffered Ca2+, and IP3 determined from their diffusion coefficients and lifetimes were 0.1 micron, 5 microns, and 24 microns, respectively. Thus, for a transient point source of messenger in cells smaller than 20 microns, IP3 is a global messenger, whereas Ca2+ acts in restricted domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allbritton, N L -- Meyer, T -- Stryer, L -- 5F32AI0814203/AI/NIAID NIH HHS/ -- MH45324/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1812-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465619" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Transporting ATPases/antagonists & inhibitors ; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology ; Chromatography, High Pressure Liquid ; Cytosol/metabolism ; Diffusion ; Inositol 1,4,5-Trisphosphate/*metabolism ; Kinetics ; Oocytes/drug effects/*metabolism ; *Second Messenger Systems ; *Signal Transduction ; Terpenes/pharmacology ; Thapsigargin ; Time Factors ; Xenopus laevis
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  • 46
    Publication Date: 1992-08-07
    Description: Immune responses in lymphocytes require cellular accumulation of large amounts of calcium (Ca2+) from extracellular sources. In the T cell tumor line Jurkat, receptors for the Ca(2+)-releasing messenger inositol 1,4,5-trisphosphate (IP3) were localized to the plasma membrane (PM). Capping of the T cell receptor-CD3 complex, which is associated with signal transduction, was accompanied by capping of IP3 receptors. The IP3 receptor on T cells appears to be responsible for the entry of Ca2+ that initiates proliferative responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khan, A A -- Steiner, J P -- Klein, M G -- Schneider, M F -- Snyder, S H -- DA-00074/DA/NIDA NIH HHS/ -- MH-18501/MH/NIMH NIH HHS/ -- P01-HL27867/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):815-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323146" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD/metabolism ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/analysis/*metabolism ; Burkitt Lymphoma ; Calcium/*metabolism ; *Calcium Channels ; Cell Line ; Cell Membrane/*metabolism ; Cells, Cultured ; Concanavalin A/pharmacology ; Fluorescent Antibody Technique ; Humans ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; Kinetics ; Receptors, Antigen, T-Cell/analysis/*metabolism ; Receptors, Cell Surface/analysis/*metabolism ; *Receptors, Cytoplasmic and Nuclear ; Second Messenger Systems ; T-Lymphocytes/*immunology
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins. By fluorescence emission anisotropy, the affinity of CaM kinase for dansylated calmodulin was measured and found to increase 1000 times after autophosphorylation of the threonine at position 286 of the protein. Autophosphorylation markedly slowed the release of bound calcium-calmodulin; the release time increased from less than a second to several hundred seconds. In essence, calmodulin is trapped by autophosphorylation. The shift in affinity does not occur in a site-directed mutant in which threonine at position 286 has been replaced by a non-phosphorylatable amino acid. These experiments demonstrate the existence of a new state in which calmodulin is bound to CaM kinase even though the concentration of calcium is basal. Calmodulin trapping provides for molecular potentiation of calcium transients and may enable detection of their frequency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, T -- Hanson, P I -- Stryer, L -- Schulman, H -- GM 40600/GM/NIGMS NIH HHS/ -- GM24032/GM/NIGMS NIH HHS/ -- MH45324/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 May 22;256(5060):1199-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317063" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding, Competitive ; Calcium/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; Calmodulin/*metabolism ; Cell Line ; Egtazic Acid/pharmacology ; Kinetics ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Protein Binding ; Protein Kinases/genetics/*metabolism ; Recombinant Proteins/metabolism ; Spectrometry, Fluorescence ; Threonine ; Time Factors ; Transfection
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-07
    Description: Analysis of neuronal migration in mouse cerebellar slice preparations by a laser scanning confocal microscope revealed that postmitotic granule cells initiate their migration only after the expression of N-type calcium channels on their plasmalemmal surface. Furthermore, selective blockade of these channels by addition of omega-conotoxin to the incubation medium curtailed cell movement. In contrast, inhibitors of L- and T-type calcium channels, as well as those of sodium and potassium channels, had no effect on the rate of granule cell migration. These results suggest that N-type calcium channels, which have been predominantly associated with neurotransmitter release in adult brain, also play a transient but specific developmental role in directed migration of immature neurons before the establishment of their synaptic circuits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Komuro, H -- Rakic, P -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323145" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/pharmacology ; Calcium Channels/drug effects/*physiology ; Cell Movement/drug effects ; Cells, Cultured ; Cerebellum/cytology/*physiology ; In Vitro Techniques ; Kinetics ; Mice ; Mollusk Venoms/pharmacology ; Neurons/cytology/drug effects/*physiology ; Peptides, Cyclic/pharmacology ; Time Factors ; *omega-Conotoxins
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  • 49
    Publication Date: 1990-02-02
    Description: A rapid increase in the RNA levels of the proto-oncogenes c-fos, c-jun, and c-myc was detected after human cytomegalovirus infection. Neither inactivation of viral infectivity with ultraviolet irradiation (with or without psoralen), nor inhibition of translation with cycloheximide or anisomycin adversely affected the enhanced expression of proto-oncogenes, even though these treatments substantially reduced or eliminated the detection of immediate early viral antigens. The increase in the RNA levels of the proto-oncogenes was prevented in the presence of alpha-amanitin or actinomycin D. Thus, expression of these oncogenes appears to be induced by events occurring before the onset of viral protein synthesis, perhaps by the interaction of viral particles with the cell surface.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boldogh, I -- AbuBakar, S -- Albrecht, T -- New York, N.Y. -- Science. 1990 Feb 2;247(4942):561-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Texas Medical Branch, Galveston 77550.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1689075" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cytomegalovirus/*genetics ; DNA-Binding Proteins/genetics ; *Gene Expression Regulation, Viral ; Humans ; Kinetics ; Lung ; Protein-Tyrosine Kinases/genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; Proto-Oncogene Proteins c-myc ; *Proto-Oncogenes ; RNA/genetics/isolation & purification ; Transcription Factors/genetics ; Transcription, Genetic
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-16
    Description: Activin, a member of the transforming growth factor beta protein family, was originally isolated from gonadal fluids and stimulates the release of pituitary follicle-stimulating hormone (FSH). Activin has numerous functions in both normal and neoplastic cells. Various cells synthesize activin and have a specific binding site for this peptide. However, the molecular basis for its actions is unknown. A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release. It is likely that the binding protein participates in the diverse regulatory actions of activin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakamura, T -- Takio, K -- Eto, Y -- Shibai, H -- Titani, K -- Sugino, H -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):836-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2106159" target="_blank"〉PubMed〈/a〉
    Keywords: Activins ; Animals ; *Carrier Proteins ; Cells, Cultured ; Female ; Follicle Stimulating Hormone/secretion ; Inhibins/isolation & purification/*metabolism/pharmacology ; Kinetics ; Molecular Weight ; Ovary/*metabolism ; Pituitary Gland/drug effects/secretion ; Protein Binding ; Rats
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  • 51
    Publication Date: 1990-05-04
    Description: Although bacteriophage T4 late promoters are selectively recognized by Escherichia coli RNA polymerase bearing a single protein encoded by T4 gene 55 (gp55), efficient transcription at these promoters requires enhancement by the three T4 DNA polymerase accessory proteins, bound to distal "mobile enhancer" sites. Two principles are shown to govern this transcriptional enhancement: (i) Promoter recognition and communication between the enhancer and the promoter require separate phage-coded proteins. Only RNA polymerase that has the T4 gene 33 protein (gp33) bound to it is subject to enhancement by the three DNA replication proteins. (ii) Transcriptional enhancement in this prokaryotic system is promoter-specific. Promoter specificity is generated by a direct competition of phage T4 gp33 and gp55 with the E. coli promoter recognition protein, sigma 70, for binding to the E. coli RNA polymerase core. Thus, polymerase that contains sigma 70 is competent to transcribe T4 early and middle genes, but lacks the ability to be enhanced by the DNA replication proteins, while polymerase that contains gp55 and gp33 is capable of enhancement via gp33, but its activity is restricted to T4 late promoters by gp55.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herendeen, D R -- Williams, K P -- Kassavetis, G A -- Geiduschek, E P -- New York, N.Y. -- Science. 1990 May 4;248(4955):573-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2185541" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/isolation & purification/*physiology ; DNA-Directed RNA Polymerases/*metabolism ; *Enhancer Elements, Genetic ; Escherichia coli/enzymology/*genetics ; Kinetics ; Models, Genetic ; *Promoter Regions, Genetic ; T-Phages/*genetics ; *Transcription Factors ; Viral Proteins/isolation & purification/*metabolism
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: The major small nuclear ribonucleoprotein particles (snRNPs) U1, U2, U4 + U6, and U5 have to be transported from the cytoplasm, where they are synthesized, to the nucleus, where they splice pre-messenger RNAs. Since the free core snRNP proteins in the cytoplasm do not enter the nucleus on their own, the nuclear location signal must either reside on the snRNA or be created as a result of snRNA-protein interaction. Here the involvement by the 5'-terminal cap of snRNA molecules in the nucleo-cytoplasmic transport of UsnRNPs has been studied by microinjection of synthetic U1 RNA molecules into frog oocytes; the U1 RNA bore either the normal cap (m3G) or a chemical derivative. Antibodies in the cytoplasm against the m3G cap inhibited the nuclear uptake of U1 snRNP. U1 RNA that was uncapped or contained an unnatural ApppG cap did not enter the nucleus, even though it carried a normal complement of protein molecules. When the ribose ring of the m3G cap was oxidized with periodate, nuclear transport of U1 snRNPs was severely inhibited. Finally, microinjection of m3G cap alone (but not m7G cap) into oocytes severely inhibited the transport of U1 snRNPs to the nucleus. These data suggest that one step in the nuclear uptake of U1 snRNPs involves the m3G cap structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, U -- Luhrmann, R -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):786-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Molekularbiologie und Tumorforschung, Phillipps-Universitat Marburg, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2143847" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Female ; Guanosine/*analogs & derivatives/physiology ; Kinetics ; Mutation ; Oocytes/*ultrastructure ; RNA Caps/*physiology ; Ribonucleoproteins/genetics/*metabolism ; Ribonucleoproteins, Small Nuclear ; Signal Transduction/*physiology ; Xenopus laevis
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  • 53
    Publication Date: 1990-02-16
    Description: Confocal laser-scanned microscopy and long-wavelength calcium (Ca2+) indicators were combined to monitor both sustained and rapidly dissipating Ca2+ gradients in voltage-clamped sympathetic neurons isolated from the bullfrog. After a brief activation of voltage-dependent Ca2+ channels, Ca2+ spreads inwardly, and reaches the center of these spherical cells in about 300 milliseconds. Although the Ca2+ redistribution in the bulk of the cytosol could be accounted for with a radial diffusion model, local nonlinearities, suggesting either nonuniform Ca2+ entry or spatial buffering, could be seen. After electrical stimulation, Ca2+ signals in the nucleus were consistently larger and decayed more slowly than those in the cytosol. A similar behavior was observed when release of intracellular Ca2+ was induced by caffeine, suggesting that in both cases large responses originate from Ca2+ release sites near or within the nucleus. These results are consistent with an amplification mechanism involving Ca2(+)-induced Ca2+ release, which could be relevant to activity-dependent, Ca2(+)-regulated nuclear events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hernandez-Cruz, A -- Sala, F -- Adams, P R -- NS1857906/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):858-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2154851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caffeine/pharmacology ; Calcium/*metabolism ; Calcium Channels/*physiology ; Cytosol/metabolism ; Fluorescent Dyes ; Ganglia, Sympathetic/drug effects/physiology ; In Vitro Techniques ; Kinetics ; Membrane Potentials ; Microscopy, Fluorescence/methods ; Neurons/cytology/drug effects/*physiology ; Rana catesbeiana
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-01-12
    Description: Experiments are presented that confirm earlier predictions that the mode of supply of reactants to a nonlinear (bio)chemical reaction determines or controls concentrations at steady states far from equilibrium. The oxidation of nicotinamide adenine dinucleotide (NADH) catalyzed by the enzyme horseradish peroxidase with continuous input of oxygen was studied; NAD+ is continuously recycled to NADH through a glucose-6-phosphate dehydrogenase system. A comparison of steady-state concentrations is made with an oscillatory oxygen input and a constant input at the same average oxygen input for both modes. By varying the frequency and amplitude of the perturbation (O2 influx), the following may be changed: the average concentration of NADH; the Gibbs free energy difference delta G of the reactants and products at steady state; the average rate of the reaction; the phase relation between the oscillatory rate and delta G; and the dissipation. These results confirm the possibility of an "alternating current chemistry," of control and optimization of thermodynamic efficiency and dissipation by means of external variation of constraints in classes of nonlinear reactions and biological pumps, and of improvements of the yield in such reactions (heterogeneous catalysis, for example).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazar, J G -- Ross, J -- New York, N.Y. -- Science. 1990 Jan 12;247(4939):189-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2294601" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Chemical Phenomena ; Chemistry ; Glucosephosphate Dehydrogenase/*metabolism ; Horseradish Peroxidase/*metabolism ; Kinetics ; NAD/*metabolism ; Oxidation-Reduction ; Oxygen/metabolism ; Peroxidases/*metabolism ; Thermodynamics
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  • 55
    Publication Date: 1990-05-11
    Description: The endosomal compartment of polarized epithelial cells is a major crossroads for membrane traffic. Proteins entering this compartment from the cell surface are sorted for transport to one of several destinations: recycling to the original cell surface, targeting to lysosomes for degradation, or transcytosis to the opposite surface. The polymeric immunoglobulin receptor (pIgR), which is normally transcytosed from the basolateral to the apical surface, was used as a model to dissect the signals that mediate this sorting event. When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis. Replacement of this serine with alanine generated a receptor that is transcytosed only slowly, and appears to be recycled. Conversely, substitution with aspartic acid (which mimics the negative charge of the phosphate group) results in rapid transcytosis. It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Casanova, J E -- Breitfeld, P P -- Ross, S A -- Mostov, K E -- R01-AI-25144/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 May 11;248(4956):742-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2110383" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine ; Animals ; Aspartic Acid ; Cell Line ; Cell Membrane/immunology/metabolism ; Endocytosis ; Immunoglobulin A/metabolism ; Kinetics ; Ligands ; Membrane Glycoproteins/metabolism ; Molecular Weight ; Mutation ; Phosphorylation ; Rats ; Receptors, Immunologic ; Secretory Component/genetics/*metabolism ; Serine
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  • 56
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-10-26
    Description: The potassium channels encoded by the Drosophila Shaker gene activate and inactivate rapidly when the membrane potential becomes more positive. Site-directed mutagenesis and single-channel patch-clamp recording were used to explore the molecular transitions that underlie inactivation in Shaker potassium channels expressed in Xenopus oocytes. A region near the amino terminus with an important role in inactivation has now been identified. The results suggest a model where this region forms a cytoplasmic domain that interacts with the open channel to cause inactivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoshi, T -- Zagotta, W N -- Aldrich, R W -- NS07158/NS/NINDS NIH HHS/ -- NS23294/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 26;250(4980):533-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University, School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2122519" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; DNA/genetics ; Drosophila melanogaster/*genetics ; Electric Conductivity ; Ion Channel Gating/drug effects/*physiology ; Kinetics ; Membrane Potentials/physiology ; Molecular Sequence Data ; Mutagenesis ; Mutagenesis, Site-Directed ; Oocytes/metabolism ; Potassium Channels/genetics/*physiology ; RNA Splicing ; Structure-Activity Relationship ; Trypsin/pharmacology ; Xenopus
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  • 57
    Publication Date: 1990-04-13
    Description: Biosynthetic studies of the prion protein (PrP) have shown that two forms of different topology can be generated from the same pool of nascent chains in cell-free translation systems supplemented with microsomal membranes. A transmembrane form is the predominant product generated in wheat germ (WG) extracts, whereas a completely translocated (secretory) form is the major product synthesized in rabbit reticulocyte lysates (RRL). An unusual topogenic sequence within PrP is now shown to direct this system-dependent difference. The actions of this topogenic sequence were independent of on-going translation and could be conferred to heterologous proteins by the engineering of a discrete set of codons. System-dependent topology conferred by addition of RRL to WG translation products suggests that this sequence interacts with one or more cytosolic factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez, C D -- Yost, C S -- Prusiner, S B -- Myers, R M -- Lingappa, V R -- AG02132/AG/NIA NIH HHS/ -- NS14069/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 13;248(4952):226-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1970195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Codon ; Cricetinae ; DNA, Viral/genetics ; Kinetics ; Mesocricetus ; Peptide Mapping ; Plasmids ; PrPSc Proteins ; Prions/*genetics ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Restriction Mapping ; Transcription, Genetic ; Viral Proteins/biosynthesis/*genetics
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  • 58
    Publication Date: 1990-10-26
    Description: The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, J H -- Ogawa, A -- Chen, L -- Orci, L -- Newgard, C B -- Alam, T -- Unger, R H -- DK02700-30/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 26;250(4980):546-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Diabetes Research, University of Texas, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237405" target="_blank"〉PubMed〈/a〉
    Keywords: 3-O-Methylglucose ; Animals ; Biological Transport ; Diabetes Mellitus/metabolism ; Diabetes Mellitus, Experimental/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; *Gene Expression ; Glucose/pharmacology ; Immunoblotting ; Insulin/secretion ; Islets of Langerhans/drug effects/*metabolism ; Kinetics ; Male ; Methylglucosides/metabolism ; Monosaccharide Transport Proteins/*genetics/metabolism ; Obesity ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred Strains ; Rats, Zucker
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  • 59
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-21
    Description: A major mechanism for generating tolerance in developing T cells is the intrathymic clonal deletion of T cells that have receptors for those self antigens that are presented on hematopoietic cells. The mechanisms of tolerance induction to antigens not expressed in the thymus remain unclear. Tolerance to self antigens can be generated extrathymically through the induction of clonal nonresponsiveness in T cells with self-reactive receptors. A second mechanism of extrathymic tolerance was identified: clonal elimination of mature T cells with self-reactive receptors that had previously displayed functional reactivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, L A -- Chin, L T -- Longo, D L -- Kruisbeek, A M -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1726-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Response Modifiers Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2125368" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antigens, CD4/analysis ; Antigens, CD8 ; Antigens, Differentiation, T-Lymphocyte/analysis ; Clone Cells ; *Immune Tolerance ; Kinetics ; *Lymphocyte Depletion ; Mice ; Mice, Inbred DBA ; Mice, Inbred Strains ; Spleen/immunology ; T-Lymphocytes/cytology/*immunology ; Thymus Gland/immunology
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  • 60
    Publication Date: 1990-07-20
    Description: Angiotensin II (AII) stimulates rapid increases in the concentration of cytosolic calcium in follicular oocytes from Xenopus laevis. This calcium response was not present in denuded oocytes, indicating that it is mediated by AII receptors on the adherent follicular cells. The endogenous AII receptors differed in their binding properties from mammalian AII receptors expressed on the oocyte surface after injection of rat adrenal messenger RNA. Also, the calcium responses to activation of the amphibian AII receptor, but not the expressed mammalian AII receptor, were blocked reversibly by octanol and intracellular acidification, treatments that inhibit cell coupling through gap junctions. In addition, AII increased the rate of progesterone-induced maturation. Thus, an AII-induced calcium-mobilizing signal is transferred from follicle cells to the oocyte through gap junctions and may play a physiological role in oocyte maturation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandberg, K -- Bor, M -- Ji, H -- Markwick, A -- Millan, M A -- Catt, K J -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):298-301.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374929" target="_blank"〉PubMed〈/a〉
    Keywords: Aequorin ; Angiotensin II/*analogs & derivatives/metabolism/*pharmacology ; Animals ; Calcium/*metabolism ; Cytosol/drug effects/metabolism ; Female ; Intercellular Junctions/drug effects/*physiology ; Kinetics ; Luminescence ; Oocytes/drug effects/*physiology ; Progesterone/pharmacology ; Receptors, Angiotensin/metabolism ; *Signal Transduction/drug effects ; Structure-Activity Relationship ; Xenopus laevis
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  • 61
    Publication Date: 1990-08-17
    Description: The interaction of a protein antigen, horse cytochrome c (cyt c), with a monoclonal antibody has been studied by hydrogen-deuterium (H-D) exchange labeling and two-dimensional nuclear magnetic resonance (2D NMR) methods. The H-exchange rate of residues in three discontiguous regions of the cyt c polypeptide backbone was slowed by factors up to 340-fold in the antibody-antigen complex compared with free cyt c. The protected residues, 36 to 38, 59, 60, 64 to 67, 100, and 101, and their hydrogen-bond acceptors, are brought together in the three-dimensional structure to form a contiguous, largely exposed protein surface with an area of about 750 square angstroms. The interaction site determined in this way is consistent with prior epitope mapping studies and includes several residues that were not previously identified. The hydrogen exchange labeling approach can be used to map binding sites on small proteins in antibody-antigen complexes and may be applicable to protein-protein and protein-ligand interactions in general.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432411/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432411/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterson, Y -- Englander, S W -- Roder, H -- GM 31847/GM/NIGMS NIH HHS/ -- GM 35926/GM/NIGMS NIH HHS/ -- R01 GM031847/GM/NIGMS NIH HHS/ -- S07-RR-05415-28/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):755-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Pennsylvania, Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1697101" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/immunology/metabolism ; Antigen-Antibody Complex ; *Binding Sites, Antibody ; Chemical Phenomena ; Chemistry ; Cytochrome c Group/*immunology ; Deuterium ; Epitopes/immunology ; Hydrogen/*metabolism ; Hydrogen Bonding ; Kinetics ; *Magnetic Resonance Spectroscopy ; Molecular Structure ; Protein Conformation
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  • 62
    Publication Date: 1990-05-18
    Description: In Saccharomyces cerevisiae, the product of the CDC25 gene controls the RAS-mediated production of adenosine 3',5'-monophosphate (cAMP). In vivo the carboxyl-terminal third of the CDC25 gene product is sufficient for the activation of adenylate cyclase. The 3'-terminal part of SCD25, a gene of S. cerevisiae structurally related to CDC25, can suppress the requirement for CDC25. Partially purified preparations of the carboxy-terminal domain of the SCD25 gene product enhanced the exchange rate of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) of pure RAS2 protein by stimulating the release of GDP. This protein fragment had a similar effect on the human c-H-ras-encoded p21 protein. Thus, the SCD25 carboxyl-terminal domain can enhance the regeneration of the active form of RAS proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crechet, J B -- Poullet, P -- Mistou, M Y -- Parmeggiani, A -- Camonis, J -- Boy-Marcotte, E -- Damak, F -- Jacquet, M -- New York, N.Y. -- Science. 1990 May 18;248(4957):866-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Biochimie, URA 240 du CNRS, Ecole Polytechnique, Palaiseau, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2188363" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Cycle Proteins ; Escherichia coli/genetics ; Fungal Proteins/genetics/*metabolism/*pharmacology ; Genes, Fungal ; Guanine Nucleotides/*metabolism ; Guanosine Diphosphate/*metabolism ; Guanosine Triphosphate/*metabolism ; Humans ; Kinetics ; Peptide Fragments/*pharmacology ; Plasmids ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins p21(ras) ; Recombinant Fusion Proteins ; Saccharomyces cerevisiae/genetics ; *Saccharomyces cerevisiae Proteins ; Transfection ; *ras Proteins ; *ras-GRF1
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  • 63
    Publication Date: 1990-08-03
    Description: Four cloned cDNAs encoding 900-amino acid putative glutamate receptors with approximately 70 percent sequence identity were isolated from a rat brain cDNA library. In situ hybridization revealed differential expression patterns of the cognate mRNAs throughout the brain. Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keinanen, K -- Wisden, W -- Sommer, B -- Werner, P -- Herb, A -- Verdoorn, T A -- Sakmann, B -- Seeburg, P H -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):556-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neuroendocrinology, University of Heidelberg, F.R.G.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2166337" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/*metabolism/physiology ; Glutamates/metabolism/pharmacology ; Ibotenic Acid/analogs & derivatives/*pharmacology ; Kainic Acid/pharmacology ; Kinetics ; Molecular Sequence Data ; *Multigene Family ; Oligonucleotide Probes ; Organ Specificity ; Oxadiazoles/pharmacology ; Oxazoles/*pharmacology ; Quisqualic Acid ; RNA, Messenger/analysis/genetics ; Rats ; Receptors, Glutamate ; Receptors, Neurotransmitter/drug effects/*genetics/physiology ; Sequence Homology, Nucleic Acid ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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  • 64
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-03
    Description: Yersinia is the genus of bacteria that is the causative agent in plague or the black death, and on several occasions this organism has killed a significant portion of the world's population. An essential virulence determinant of Yersinia was shown to be a protein tyrosine phosphatase. The recombinant 50-kilodalton Yersinia phosphatase had a specificity for removal of phosphate from Tyr-containing as opposed to Ser/Thr-containing phosphopeptides and proteins. Site-directed mutagenesis was used to show that the Yersinia phosphatase possesses an essential Cys residue required for catalysis. Amino acids surrounding an essential Cys residue are highly conserved, as are other amino acids in the Yersinia and mammalian protein tyrosine phosphatases, suggesting that they use a common catalytic mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guan, K L -- Dixon, J E -- 18849/PHS HHS/ -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):553-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Purdue University, West Lafayette, IN 47907.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2166336" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Kinetics ; Molecular Sequence Data ; Phosphoprotein Phosphatases/*genetics/metabolism ; Protein Tyrosine Phosphatases ; Sequence Homology, Nucleic Acid ; Virulence/genetics ; Yersinia/enzymology/genetics/*pathogenicity
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  • 65
    Publication Date: 1992-05-08
    Description: Voltage-sensitive sodium channels are responsible for the initiation and propagation of the action potential and therefore are important for neuronal excitability. Complementary DNA clones encoding the beta 1 subunit of the rat brain sodium channel were isolated by a combination of polymerase chain reaction and library screening techniques. The deduced primary structure indicates that the beta 1 subunit is a 22,851-dalton protein that contains a single putative transmembrane domain and four potential extracellular N-linked glycosylation sites, consistent with biochemical data. Northern blot analysis reveals a 1,400-nucleotide messenger RNA in rat brain, heart, skeletal muscle, and spinal cord. Coexpression of beta 1 subunits with alpha subunits increases the size of the peak sodium current, accelerates its inactivation, and shifts the voltage dependence of inactivation to more negative membrane potentials. These results indicate that the beta 1 subunit is crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the rat brain sodium channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Isom, L L -- De Jongh, K S -- Patton, D E -- Reber, B F -- Offord, J -- Charbonneau, H -- Walsh, K -- Goldin, A L -- Catterall, W A -- NS15751/NS/NINDS NIH HHS/ -- NS25704/NS/NINDS NIH HHS/ -- NS26729/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 May 8;256(5058):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1375395" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Brain/*physiology ; Cloning, Molecular ; DNA/genetics/isolation & purification ; Female ; Kinetics ; Macromolecular Substances ; Membrane Potentials ; Molecular Sequence Data ; Oocytes/physiology ; Polymerase Chain Reaction/methods ; Protein Conformation ; RNA/genetics/isolation & purification ; RNA, Messenger/genetics ; Rats ; Sodium Channels/*genetics/*physiology ; Voltage-Gated Sodium Channel beta-1 Subunit ; Xenopus
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  • 66
    Publication Date: 1992-04-17
    Description: An antibody generated against a neutral phosphonate diester transition-state analog was found to catalyze the aminoacylation of the 3'-hydroxyl group of thymidine with an alanyl ester. A comparison of the apparent second-order rate constant of the antibody-catalyzed reaction [5.4 x 10(4) molar-1 minute-1 (M-1 min-1)] with that of the uncatalyzed reaction (2.6 x 10(-4) M-1 min-1) revealed this to be a remarkably efficient catalyst. Moreover, although the concentration of water (55 M) greatly exceeds that of the secondary alcohol, the antibody selectively catalyzes acyl transfer to thymidine. The antibody exhibits sequential binding, with Michaelis constants of 770 microM and 260 microM for acyl acceptor and donor, respectively, and a dissociation constant of 240 pM for hapten. This antibody-catalyzed reaction provides increased insight into the requirements for efficient aminoacylation catalysts and may represent a first step toward the generation of "aminoacyl transfer RNA synthetases" with novel specificities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobsen, J R -- Prudent, J R -- Kochersperger, L -- Yonkovich, S -- Schultz, P G -- AI24695/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):365-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566082" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Alanine/*metabolism ; Amino Acyl-tRNA Synthetases/metabolism ; Antibodies, Monoclonal/*metabolism ; *Catalysis ; Chromatography, High Pressure Liquid ; Esterification ; Haptens/immunology ; Hemocyanin/immunology ; Kinetics ; Organophosphonates/*immunology ; Serum Albumin, Bovine/immunology ; Thymidine/*metabolism
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  • 67
    Publication Date: 1992-11-20
    Description: Fluorescence-detected stopped-flow and equilibrium methods have been used to study the mechanism for binding of pyrene (pyr)-labeled RNA oligomer substrates to the ribozyme (catalytic RNA) from Tetrahymena thermophila. The fluorescence of these substrates increases up to 25-fold on binding to the ribozyme. Stopped-flow experiments provide evidence that pyr experiences at least three different microenvironments during the binding process. A minimal mechanism is presented in which substrate initially base pairs to ribozyme and subsequently forms tertiary contacts in an RNA folding step. All four microscopic rate constants are measured for ribozyme binding of pyrCCUCU.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bevilacqua, P C -- Kierzek, R -- Johnson, K A -- Turner, D H -- GM 22939/GM/NIGMS NIH HHS/ -- GM44613/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Nov 20;258(5086):1355-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Rochester, NY 14627.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1455230" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hydrogen Bonding ; Kinetics ; *RNA Splicing ; RNA, Catalytic/*metabolism ; RNA, Guide/*metabolism ; RNA, Protozoan/*metabolism ; RNA, Ribosomal/*metabolism ; Substrate Specificity ; Tetrahymena thermophila ; Thermodynamics
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  • 68
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-07
    Description: The signal transduction mechanisms of interferons (IFNs) remain unclear partly because no effect of IFN has been reproducible in a cell-free system. IFN-alpha rapidly induces the transcription of a set of early response genes, and a multicomponent transcriptional activator, interferon stimulated gene factor 3 (ISGF3), is activated within minutes after binding of IFN-alpha to its receptor. A system was developed in which IFN-alpha activated ISGF3 in homogenates of HeLa cells. Subcellular fractionation revealed that incubation of a plasma membrane-enriched fraction with IFN-alpha was sufficient to activate the regulatory subcomponent of ISGF3.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉David, M -- Larner, A C -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):813-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1496402" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell-Free System ; DNA-Binding Proteins/biosynthesis/isolation & purification/*metabolism ; HeLa Cells ; Humans ; Interferon-Stimulated Gene Factor 3 ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; Interferon-alpha/*pharmacology ; Interferon-gamma/pharmacology ; Kinetics ; Molecular Sequence Data ; Molecular Weight ; Oligonucleotide Probes ; Transcription Factors/biosynthesis/isolation & purification/*metabolism ; Transcription, Genetic/*drug effects
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-03
    Description: Although tetrameric hemoglobin has been studied extensively as a prototype for understanding mechanisms of allosteric regulation, the functional and structural properties of its eight intermediate ligation forms have remained elusive. Recent experiments on the energetics of cooperativity of these intermediates, along with assignments of their quaternary structures, have revealed that the allosteric mechanism is controlled by a previously unrecognized symmetry feature: quaternary switching from form T to form R occurs whenever heme-site binding creates a tetramer with at least one ligated subunit on each dimeric half-molecule. This "symmetry rule" translates the configurational isomers of heme-site ligation into six observed switchpoints of quaternary transition. Cooperativity arises from both "concerted" quaternary switching and "sequential" modulation of binding within each quaternary form, T and R. Binding affinity is regulated through a hierarchical code of tertiary-quaternary coupling that includes the classical allosteric models as limiting cases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ackers, G K -- Doyle, M L -- Myers, D -- Daugherty, M A -- P01-HL40453/HL/NHLBI NIH HHS/ -- R37-GM24486/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):54-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553532" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Calorimetry ; Circular Dichroism ; Hemoglobins/*chemistry/genetics/metabolism ; Kinetics ; Ligands ; Macromolecular Substances ; Models, Molecular ; Mutation ; Oxyhemoglobins/chemistry/metabolism ; Protein Conformation ; Thermodynamics
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  • 70
    Publication Date: 1992-06-05
    Description: The D and L forms of the enzyme HIV-1 protease have been prepared by total chemical synthesis. The two proteins had identical covalent structures. However, the folded protein-enzyme enantiomers showed reciprocal chiral specificity on peptide substrates. That is, each enzyme enantiomer cut only the corresponding substrate enantiomer. Reciprocal chiral specificity was also evident in the effect of enantiomeric inhibitors. These data imply that the folded forms of the chemically synthesized D- and L-enzyme molecules are mirror images of one another in all elements of the three-dimensional structure. Enantiomeric proteins are expected to display reciprocal chiral specificity in all aspects of their biochemical interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milton, R C -- Milton, S C -- Kent, S B -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1445-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1604320" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Amino Acids ; HIV Protease/chemical synthesis/*chemistry/*metabolism ; Kinetics ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Oligopeptides/pharmacology ; Protein Conformation ; Stereoisomerism ; Substrate Specificity ; X-Ray Diffraction
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-09
    Description: Migration of human polymorphonuclear neutrophils on vitronectin is dependent on repeated transient increases in the concentration of intracellular free calcium ([Ca2+]i). A specific peptide inhibitor of the Ca(2+)-calmodulin-dependent phosphatase calcineurin was introduced into the cytoplasm of neutrophils. The peptide inhibited neutrophil migration on vitronectin by interfering with the release of the cells from sites of attachment. A similar reduction in motility on vitronectin occurred when cells were treated with the immunosuppressant FK506, which also inhibits calcineurin when bound to its binding protein, FKBP. These results indicate that a rise in [Ca2+]i reduces integrin-mediated adhesion to vitronectin by a mechanism that requires calcineurin activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hendey, B -- Klee, C B -- Maxfield, F R -- GM14150/GM/NIGMS NIH HHS/ -- GM34770/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 9;258(5080):296-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1384129" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Aminoquinolines/pharmacology ; Calcineurin ; Calmodulin-Binding Proteins/*antagonists & inhibitors/physiology ; Carrier Proteins/metabolism ; Chemotaxis, Leukocyte/*drug effects ; Ethers, Cyclic/pharmacology ; *Glycoproteins ; Humans ; Kinetics ; Molecular Sequence Data ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/cytology/drug effects/*physiology ; Okadaic Acid ; Peptide Fragments/pharmacology ; Peptides/pharmacology ; Phosphoprotein Phosphatases/*antagonists & inhibitors/physiology ; Phosphorylation ; Tacrolimus/pharmacology ; Tacrolimus Binding Proteins ; Vitronectin
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-11-30
    Description: Deep inflation of the lung stimulates surfactant secretion by unknown mechanisms. The hypothesis that mechanical distension directly stimulates type II cells to secrete surfactant was tested by stretching type II cells cultured on silastic membranes. The intracellular Ca2+ concentration was measured in single cells, before and after stretching. A single stretch of alveolar type II cells caused a transient (less than 60 seconds) increase in cytosolic Ca2+ followed by a sustained (15 to 30 minutes) stimulation of surfactant secretion. Both Ca2+ mobilization and exocytosis exhibited dose-dependence to the magnitude of the stretch-stimulus. Thus, mechanical factors can trigger complex cellular events in nonneuron, nonmuscle cells and may be involved in regulating normal lung functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wirtz, H R -- Dobbs, L G -- HL-24075/HL/NHLBI NIH HHS/ -- HL-34356/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 30;250(4985):1266-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California, San Francisco 94143-0130.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2173861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Calcium/*metabolism ; Cells, Cultured ; Cyclic AMP/metabolism ; Epithelium/physiology ; *Exocytosis ; Kinetics ; Phosphatidylcholines/secretion ; Proteolipids/pharmacology ; Pulmonary Alveoli/*physiology ; Pulmonary Surfactant-Associated Proteins ; Pulmonary Surfactants/pharmacology/secretion ; Rats ; Surface Properties ; Tetradecanoylphorbol Acetate/pharmacology
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-24
    Description: During fruiting body morphogenesis of Myxococcus xanthus, cell movement is required for transmission of C-factor, a short range intercellular signaling protein necessary for sporulation and developmental gene expression. Nonmotile cells fail to sporulate and to express C-factor-dependent genes, but both defects were rescued by a simple manipulation of cell position that oriented the cells in aligned, parallel groups. A similar pattern of aligned cells normally results from coordinated recruitment of wildtype cells into multicellular aggregates, which later form mature fruiting bodies. It is proposed that directed cell movement establishes critical contacts between adjacent cells, which are required for efficient intercellular C-factor transmission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, S K -- Kaiser, D -- AGO 2908/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 24;249(4971):926-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2118274" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins ; Cell Differentiation ; Cell Division ; Cell Movement ; Kinetics ; Morphogenesis ; Myxococcales/*growth & development/physiology/ultrastructure ; Spores, Bacterial/physiology
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  • 74
    Publication Date: 1990-12-07
    Description: A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (greater than 8000) in culture.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merluzzi, V J -- Hargrave, K D -- Labadia, M -- Grozinger, K -- Skoog, M -- Wu, J C -- Shih, C K -- Eckner, K -- Hattox, S -- Adams, J -- HB 67027/HB/NHLBI NIH HHS/ -- HL 42257/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1411-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1701568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology ; Cell Line ; HIV-1/*drug effects/enzymology/physiology ; Humans ; Kinetics ; Molecular Structure ; Nevirapine ; Nucleic Acid Synthesis Inhibitors ; Pyridines/chemical synthesis/*pharmacology ; *Reverse Transcriptase Inhibitors ; Virus Replication/*drug effects
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  • 75
    Publication Date: 1990-10-05
    Description: To facilitate functional and mechanistic studies of receptor-G protein interactions, [corrected] the human beta 2-adrenergic receptor (h beta-AR) has been expressed in Saccharomyces cerevisiae. This was achieved by placing a modified h beta-AR gene under control of the galactose-inducible GAL1 promoter. After induction by galactose, functional h beta-AR was expressed at a concentration several hundred times as great as that found in any human tissue. As determined from competitive ligand binding experiments, h beta-AR expressed in yeast displayed characteristic affinities, specificity, and stereoselectivity. Partial activation of the yeast pheromone response pathway by beta-adrenergic receptor agonists was achieved in cells coexpressing h beta-AR and a mammalian G protein (Gs) alpha subunit-demonstrating that these components can couple to each other and to downstream effectors when expressed in yeast. This in vivo reconstitution system provides a new approach for examining ligand binding and G protein coupling to cell surface receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, K -- Dohlman, H G -- Thorner, J -- Caron, M G -- Lefkowitz, R J -- GM21841/GM/NIGMS NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 5;250(4977):121-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine (Cardiology), Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2171146" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Membrane/physiology ; GTP-Binding Proteins/genetics/*physiology ; Gene Expression ; Humans ; Iodocyanopindolol ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Pindolol/analogs & derivatives/metabolism ; Plasmids ; Promoter Regions, Genetic ; Receptors, Adrenergic, beta/genetics/metabolism/*physiology ; Recombinant Fusion Proteins/metabolism ; Restriction Mapping ; Saccharomyces cerevisiae/genetics/*physiology ; *Signal Transduction
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-31
    Description: Major histocompatibility complex (MHC) molecules are exposed to large quantities of self and nonself antigens. It is not known what fraction of MHC molecules needs to be occupied by antigen to induce a T cell response. A quantitative study of naturally processed antigen indicated that T cells could be activated when only 0.03 percent of the total I-Ed purified from antigen-presenting cells (APCs) was occupied with antigen. B cells and macrophages processed hen egg lysozyme (HEL) with different efficiencies, but similar degrees of occupancy were required for T cell stimulation. Higher occupancy was needed for I-Ed-transfected L cells, possibly reflecting the requirement for other accessory molecules for efficient APC-T cell interaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Demotz, S -- Grey, H M -- Sette, A -- AI 09758/AI/NIAID NIH HHS/ -- AI 18634/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1028-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cytel Corporation, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2118680" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/*immunology ; B-Lymphocytes/immunology ; Cell Line ; Genes, MHC Class II ; Histocompatibility Antigens Class II/*immunology ; Kinetics ; *Lymphocyte Activation ; Lymphoma ; Macrophages/immunology ; Muramidase/immunology ; T-Lymphocytes/*immunology ; Transfection
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  • 77
    Publication Date: 1990-09-28
    Description: In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sommer, B -- Keinanen, K -- Verdoorn, T A -- Wisden, W -- Burnashev, N -- Herb, A -- Kohler, M -- Takagi, T -- Sakmann, B -- Seeburg, P H -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1580-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology, University of Heidelberg, F.R.G.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1699275" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/*metabolism ; DNA/genetics ; Exons ; Genomic Library ; Glutamates/*metabolism/pharmacology ; Ibotenic Acid/*analogs & derivatives/metabolism/pharmacology ; Ion Channels/*physiology ; Kinetics ; Molecular Sequence Data ; Oligonucleotide Probes ; Organ Specificity ; *RNA Splicing ; RNA, Messenger/*genetics ; Rats ; Receptors, AMPA ; Receptors, Glutamate ; Receptors, Neurotransmitter/drug effects/*genetics/physiology ; Recombinant Proteins/metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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  • 78
    Publication Date: 1990-12-07
    Description: The polymerization of actin filaments is involved in growth, movement, and cell division. It has been shown that actin polymerization is controlled by gelsolin, whose interactions with actin are activated by calcium ion (Ca2+) and inhibited by membrane polyphosphoinositides (PPI). A smaller Ca2(+)- and PPI-regulated protein, gCap39, which has 49% sequence identity with gelsolin, has been identified by cDNA cloning and protein purification. Like gelsolin, gCap39 binds to the fast-growing (+) end of actin filaments. However, gCap39 does not sever actin filaments and can respond to Ca2+ and PPI transients independently, under conditions in which gelsolin is ineffective. The coexistence of gCap39 with gelsolin should allow precise regulation of actin assembly at the leading edge of the cell.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, F X -- Johnston, P A -- Sudhof, T C -- Yin, H L -- HL 29113/HL/NHLBI NIH HHS/ -- HL 39644/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1413-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2255912" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; DNA/genetics/isolation & purification ; Gene Library ; Humans ; Kidney/metabolism ; Kinetics ; Macrophages/metabolism ; Mice ; Microfilament Proteins/genetics/isolation & purification/*metabolism ; Molecular Sequence Data ; *Nuclear Proteins ; Sequence Homology, Nucleic Acid
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-21
    Description: Voltage-activated calcium channels open and close, or gate, according to molecular transition rates that are regulated by transmembrane voltage and neurotransmitters. Here evidence for the control of gating by calcium was found in electrophysiological records of single, L-type calcium channels in heart cells. Conditional open probability analysis revealed that calcium entry during the opening of a single channel produces alterations in gating transition rates that evolve over the course of hundreds of milliseconds. Such alteration of calcium-channel gating by entry of a favored permeant ion provides a mechanism for the short-term modulation of single-ion channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yue, D T -- Backx, P H -- Imredy, J P -- 5-T32-GM07057/GM/NIGMS NIH HHS/ -- R29-HL43307/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1735-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2176745" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Calcium/*metabolism/pharmacology ; Calcium Channels/drug effects/*physiology ; Guinea Pigs ; Heart/*physiology ; In Vitro Techniques ; *Ion Channel Gating/drug effects ; Kinetics ; Membrane Potentials/drug effects ; Probability ; Ventricular Function
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-23
    Description: The atrionatriuretic peptide (ANP) is released from atrial cells in response to increased extracellular fluid volume and reduces sodium absorption by the kidney, thus reducing the blood volume. In this report, ANP suppressed the calcium and sodium currents in rat and guinea pig ventricular myocytes. The suppression of sodium current was caused by enhanced permeability of the sodium channel to calcium without significant changes in the kinetics or the tetrodotoxin sensitivity of the channel. Thus, ANP may regulate the sodium channel by altering its cationic selectivity site to calcium, thereby repressing the sodium current. The suppression of sodium and calcium channels and the resultant depressed excitability of the atrial cells may help to regulate ANP secretion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sorbera, L A -- Morad, M -- HL16152/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):969-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2154853" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atrial Natriuretic Factor/*pharmacology ; Calcium/metabolism ; Calcium Channels/*metabolism ; Electric Conductivity ; Guinea Pigs ; Heart Ventricles ; Kinetics ; Myocardium/*metabolism ; Permeability ; Rats ; Sodium Channels/drug effects/*metabolism ; Tetrodotoxin/pharmacology
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  • 81
    Publication Date: 1990-12-21
    Description: The progesterone receptor (PR) in the chicken oviduct is a phosphoprotein that regulates gene transcription in the presence of progesterone. Treatment with progesterone in vivo stimulates phosphorylation of the progesterone receptor. With transient transfection assays, the present work has tested whether phosphorylation participates in the regulation of PR-mediated transcription. Treatment with 8-bromo-cyclic adenosine monophosphate (8-Br cAMP), a stimulator of cAMP-dependent protein kinase [protein kinase A (PKA)], mimicked progesterone-dependent, receptor-mediated transcription in the absence of progesterone. Inhibition of PKA blocked hormone action. Treatment with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, stimulated transcription in a manner similar to that of progesterone. These observations suggest that phosphorylation of the PR or other proteins in the transcription complex can modulate PR-mediated transcription in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denner, L A -- Weigel, N L -- Maxwell, B L -- Schrader, W T -- O'Malley, B W -- HD-07857/HD/NICHD NIH HHS/ -- HD-22061/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1740-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2176746" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Cell Line ; Chickens ; Female ; Gene Expression Regulation ; Kinetics ; Oviducts/metabolism ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Phosphorylation ; Progesterone/*pharmacology ; Receptors, Progesterone/*metabolism ; *Transcription, Genetic/drug effects ; Transfection
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  • 82
    Publication Date: 1990-08-03
    Description: A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erickson, J -- Neidhart, D J -- VanDrie, J -- Kempf, D J -- Wang, X C -- Norbeck, D W -- Plattner, J J -- Rittenhouse, J W -- Turon, M -- Wideburg, N -- AI 27220/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):527-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer-Assisted Molecular Design, Abbott Laboratories, Abbott Park, IL 60064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2200122" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Drug Design ; Endopeptidases/*metabolism ; Gene Products, pol/*metabolism ; HIV Protease ; HIV-1/*enzymology ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Protease Inhibitors/*pharmacology ; Protein Conformation ; Sugar Alcohols/*pharmacology ; Valine/*analogs & derivatives/pharmacology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 83
    Publication Date: 1990-06-29
    Description: The presence of endothelin, a vasoconstrictor peptide, in the hypothalamus and posterior pituitary suggests that it also regulates neural and other nonvascular target cells. In pituitary gonadotrophs, low doses of endothelin evoked oscillations in the intracellular calcium concentration, and high doses induced a biphasic calcium response. Mobilization of intracellular calcium predominated during the spike phase of the calcium response to endothelin, whereas calcium entry through dihydropyridine-sensitive channels contributed to both the spike and plateau phases of the calcium response. Endothelin was a potent as hypothalamic gonadotropin-releasing hormone (GnRH) in stimulation of gonadotropin release in perifused pituitary cells. Endothelin bound specifically to pituitary cells with a dissociation constant of 70 picomolar, and induced rapid formation of inositol trisphosphate and diacyglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent to the GnRH receptor, endothelin and GnRH appeared to have a common signal transduction mechanism. These observations suggest that endothelin can act as a neuropeptide to regulate anterior pituitary function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stojilkovic, S S -- Merelli, F -- Iida, T -- Krsmanovic, L Z -- Catt, K J -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cells, Cultured ; Cytosol/metabolism ; Endothelins ; Endothelium, Vascular ; Female ; Follicle Stimulating Hormone/*secretion ; Gonadotropin-Releasing Hormone/pharmacology ; Kinetics ; Luteinizing Hormone/*secretion ; Male ; Nifedipine/pharmacology ; Orchiectomy ; Peptides/metabolism/*pharmacology ; Pituitary Gland, Anterior/drug effects/*metabolism/secretion ; Rats ; Rats, Inbred Strains ; Receptors, Cell Surface/metabolism ; Receptors, Endothelin ; Reference Values
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  • 84
    Publication Date: 1990-08-31
    Description: Three closely related genes, GluR1, GluR2, and GluR3, encode receptor subunits for the excitatory neurotransmitter glutamate. The proteins encoded by the individual genes form homomeric ion channels in Xenopus oocytes that are sensitive to glutamatergic agonists such as kainate and quisqualate but not to N-methyl-D-aspartate, indicating that binding sites for kainate and quisqualate exist on single receptor polypeptides. In addition, kainate-evoked conductances are potentiated in oocytes expressing two or more of the cloned receptor subunits. Electrophysiological responses obtained with certain subunit combinations show agonist profiles and current-voltage relations that are similar to those obtained in vivo. Finally, in situ hybridization histochemistry reveals that these genes are transcribed in shared neuroanatomical loci. Thus, as with gamma-aminobutyric acid, glycine, and nicotinic acetylcholine receptors, native kainate-quisqualate-sensitive glutamate receptors form a family of heteromeric proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boulter, J -- Hollmann, M -- O'Shea-Greenfield, A -- Hartley, M -- Deneris, E -- Maron, C -- Heinemann, S -- NS11549/NS/NINDS NIH HHS/ -- NS28709/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1033-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, San Diego, CA 92138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2168579" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cloning, Molecular ; Gene Expression ; Glutamates/metabolism ; Hippocampus/metabolism ; Kinetics ; Macromolecular Substances ; Membrane Potentials ; Molecular Sequence Data ; *Multigene Family ; Oocytes/physiology ; Rats ; Receptors, Glutamate ; Receptors, Neurotransmitter/*genetics/physiology ; Sequence Homology, Nucleic Acid ; Transcription, Genetic
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  • 85
    Publication Date: 1990-11-30
    Description: Phospholipase C-gamma 1 (PLC-gamma 1), an isozyme of the phosphoinositide-specific phospholipase C family, which occupies a central role in hormonal signal transduction pathways, is an excellent substrate for the epidermal growth factor (EGF) receptor tyrosine kinase. Epidermal growth factor elicits tyrosine phosphorylation of PLC-gamma 1 and phosphatidylinositol 4,5-bisphosphate hydrolysis in various cell lines. The ability of tyrosine phosphorylation to activate the catalytic activity of PLC-gamma 1 was tested. Tyrosine phosphorylation in intact cells or in vitro increased the catalytic activity of PLC-gamma 1. Also, treatment of EGF-activated PLC-gamma 1 with a tyrosine-specific phosphatase substantially decreased the catalytic activity of PLC-gamma 1. These results suggest that the EGF-stimulated formation of inositol 1,4,5-trisphosphate and diacylglycerol in intact cells results, at least in part, from catalytic activation of PLC-gamma 1 through tyrosine phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishibe, S -- Wahl, M I -- Hernandez-Sotomayor, S M -- Tonks, N K -- Rhee, S G -- Carpenter, G -- CA43720/CA/NCI NIH HHS/ -- GMO7347/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 30;250(4985):1253-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1700866" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Diglycerides/metabolism ; Enzyme Activation/drug effects ; Epidermal Growth Factor/pharmacology ; Immunosorbent Techniques ; Inositol 1,4,5-Trisphosphate/metabolism ; Isoenzymes/*metabolism ; Kinetics ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositol Diacylglycerol-Lyase ; Phosphatidylinositols/metabolism ; Phosphoric Diester Hydrolases/*metabolism ; Phosphorylation ; Phosphotyrosine ; Protein-Tyrosine Kinases/metabolism ; Receptor, Epidermal Growth Factor ; Signal Transduction ; Tyrosine/*analogs & derivatives/metabolism
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  • 86
    Publication Date: 1990-06-29
    Description: Platelet-derived growth factor (PDGF) induction of DNA synthesis is believed to involve activation of phospholipase C (PLC) and subsequent accumulation of inositol 1,4,5-triphosphate [I(1,4,5)P3], increase in intracellular Ca2+, activation of protein kinase C (PKC), and receptor down regulation. Generation of these events is triggered by the tyrosine protein kinase (TPK) activity of the PDGF receptor. The TPK inhibitor genistein blocked PDGF induction of these events, including DNA synthesis, with the exception of receptor down regulation. PDGF-induced phosphotyrosine phosphorylations, including receptor autophosphorylation, were inhibited by genistein. Removal of genistein and PDGF resulted in DNA synthesis without the occurrence of PLC activation. These findings indicate that these early events, with the exception of receptor down regulation, are not necessary for PDGF-induced DNA synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, T D -- Dean, N M -- Mordan, L J -- Lau, A F -- Kanemitsu, M Y -- Boynton, A L -- CA 2942/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1660-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163545" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cells, Cultured ; Chlorides/pharmacology ; DNA Replication/*drug effects ; Dimethyl Sulfoxide/pharmacology ; Enzyme Activation ; Genistein ; Inositol Phosphates/metabolism ; Isoflavones/pharmacology ; Kinetics ; Lithium/pharmacology ; Lithium Chloride ; Mice ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositols/metabolism ; Phosphorylation ; Platelet-Derived Growth Factor/*pharmacology ; Protein Kinase C/metabolism ; Protein-Tyrosine Kinases/metabolism ; Type C Phospholipases/*metabolism
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  • 87
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-07
    Description: Efficient transport of class I major histocompatibility complex molecules to the cell surface requires association of the class I heavy chain with endogenous peptide and the class I light chain, beta 2-microglobulin (beta 2M). A mutant cell line deficient in beta 2M transports low amounts of nonpeptide-associated heavy chains to the cell surface that can associate with exogenously provided beta 2M and synthetic peptide antigens. Normal beta 2M-sufficient cells grown in serum-free media devoid of beta 2M also require an exogenous source of beta 2M to efficiently bind synthetic peptide. Thus, class I molecules on normal cells do not spontaneously bind or exchange peptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vitiello, A -- Potter, T A -- Sherman, L A -- AI-25280/AI/NIAID NIH HHS/ -- CA-25803/CA/NCI NIH HHS/ -- CA-49394/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1423-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cytel Corporation, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2124002" target="_blank"〉PubMed〈/a〉
    Keywords: Abelson murine leukemia virus/genetics ; Animals ; Antibodies ; Biological Transport ; Cell Line ; Cell Membrane/immunology ; Cell Transformation, Neoplastic ; Cytotoxicity, Immunologic ; Histocompatibility Antigens Class I/analysis/*metabolism ; Immunoglobulin Heavy Chains/metabolism ; Kinetics ; Mice ; Mice, Inbred Strains ; T-Lymphocytes, Cytotoxic/immunology ; beta 2-Microglobulin/genetics/*metabolism
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  • 88
    Publication Date: 1990-09-21
    Description: The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schumann, R R -- Leong, S R -- Flaggs, G W -- Gray, P W -- Wright, S D -- Mathison, J C -- Tobias, P S -- Ulevitch, R J -- AI 15136/AI/NIAID NIH HHS/ -- AI 25563/AI/NIAID NIH HHS/ -- GM 28485/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1429-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2402637" target="_blank"〉PubMed〈/a〉
    Keywords: *Acute-Phase Proteins ; Amino Acid Sequence ; Animals ; Base Sequence ; Blood Proteins/*genetics ; Carrier Proteins/*genetics/metabolism ; Gene Library ; Humans ; Kinetics ; Lipid A/metabolism ; Lipopolysaccharides/*metabolism/pharmacology ; Male ; *Membrane Glycoproteins ; Molecular Sequence Data ; Oligonucleotide Probes ; Rabbits ; Sequence Homology, Nucleic Acid ; Sheep ; Staphylococcus aureus ; Tumor Necrosis Factor-alpha/biosynthesis
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  • 89
    Publication Date: 1990-08-03
    Description: Human immunodeficiency virus (HIV) frequently causes neurological dysfunction and is abundantly expressed in the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients with HIV encephalitis or myelopathy. The virus is found mostly in cells of the monocyte-macrophage lineage within the CNS, but the possibility of infection of other glial cells has been raised. Therefore, the effects of different HIV-1 and HIV-2 strains were studied in primary cultures of adult human brain containing microglial cells, the resident CNS macrophages, and astrocytes. These cultures could be productively infected with macrophage-adapted HIV-1 isolates but not with T lymphocyte-adapted HIV-1 isolates or two HIV-2 isolates. As determined with a triple-label procedure, primary astrocytes did not express HIV gag antigens and remained normal throughout the 3-week course of infection. In contrast, virus replicated in neighboring microglial cells, often leading to their cell fusion and death. The death of microglial cells, which normally serve immune functions in the CNS, may be a key factor in the pathogenesis of AIDS encephalitis or myelopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watkins, B A -- Dorn, H H -- Kelly, W B -- Armstrong, R C -- Potts, B J -- Michaels, F -- Kufta, C V -- Dubois-Dalcq, M -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):549-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2200125" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain/*microbiology ; Cells, Cultured ; Fluorescent Antibody Technique ; HIV-1/pathogenicity/*physiology ; HIV-2/pathogenicity/physiology ; Humans ; Kinetics ; Neuroglia/*microbiology ; Species Specificity ; Virus Replication
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  • 90
    Publication Date: 1990-05-04
    Description: A low molecular weight serine protease inhibitor (TAP) was purified from extracts of the soft tick, Ornithodoros moubata. The peptide is a slow, tight-binding inhibitor, specific for factor Xa (Ki = 0.588 +/- 0.054 nM). The inhibitor also acts as an anticoagulant in several human plasma clotting assays in vitro. Its amino acid sequence (60 residues) has limited homology to the Kunitz-type inhibitors. However, unlike other inhibitors of this class, TAP inhibits only factor Xa. It had no effect at a 300-fold molar excess on factor VIIa, kallikrein, trypsin, chymotrypsin, thrombin, urokinase, plasmin, tissue plasminogen activator, elastase, or Staphylococcus aureus V8 protease. TAP's specificity and size suggest that it may have therapeutic value as an anticoagulant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waxman, L -- Smith, D E -- Arcuri, K E -- Vlasuk, G P -- New York, N.Y. -- Science. 1990 May 4;248(4955):593-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Chemistry Department, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2333510" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arthropod Proteins ; Blood Coagulation Tests ; Chromatography, Gel ; *Factor Xa Inhibitors ; Humans ; Kinetics ; Molecular Sequence Data ; Peptides/*isolation & purification/pharmacology ; Sequence Homology, Nucleic Acid ; Serine Proteinase Inhibitors/*isolation & purification ; Ticks/*analysis
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  • 91
    Publication Date: 1992-12-18
    Description: Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Devane, W A -- Hanus, L -- Breuer, A -- Pertwee, R G -- Stevenson, L A -- Griffin, G -- Gibson, D -- Mandelbaum, A -- Etinger, A -- Mechoulam, R -- DA 6481/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1992 Dec 18;258(5090):1946-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Natural Products, Medical Faculty, Hebrew University, Jerusalem, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1470919" target="_blank"〉PubMed〈/a〉
    Keywords: Amides/chemistry/*isolation & purification/pharmacology ; Animals ; *Arachidonic Acids ; Binding, Competitive ; Brain/*metabolism ; Brain Chemistry ; Cannabinoids/metabolism ; Chromatography, Thin Layer ; Endocannabinoids ; Fatty Acids, Unsaturated/chemistry/*isolation & purification/pharmacology ; Gas Chromatography-Mass Spectrometry ; Kinetics ; Polyunsaturated Alkamides ; Receptors, Cannabinoid ; Receptors, Drug/*metabolism ; Swine
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  • 92
    Publication Date: 1992-12-11
    Description: Class II major histocompatibility complexes bind peptides in an endosome-like compartment. When the class II null cell line 721.174 was transfected with class II DR3 genes, DR molecules were produced in normal amounts. However, the DR molecules were abnormally conformed and unstable because deletion of an antigen-processing gene had impaired intracellular formation of most class II-peptide complexes. Yet, 70 percent of the DR molecules still bore peptides, 80 percent of which were 21- to 24-amino acid fragments of the class II-associated invariant chain. These peptides were rare on DR3 from control cells. Thus, a defect in the main antigen-processing pathway revealed a process in which DR molecules bind long peptides derived from proteins present in the same compartment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sette, A -- Ceman, S -- Kubo, R T -- Sakaguchi, K -- Appella, E -- Hunt, D F -- Davis, T A -- Michel, H -- Shabanowitz, J -- Rudersdorf, R -- AI15486/AI/NIAID NIH HHS/ -- AI18634/AI/NIAID NIH HHS/ -- GM37537/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1801-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, University of Wisconsin, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465617" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Line ; Gene Deletion ; *Genes, MHC Class II ; HLA-DR Antigens/*genetics/*metabolism ; HLA-DR3 Antigen/*genetics/metabolism ; Humans ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Peptides/*metabolism ; Transfection
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  • 93
    Publication Date: 1992-12-18
    Description: The parasitic nematode Ascaris infests a billion people worldwide. Much of its proliferative success is due to prodigious egg production, up to 10(6) sterol-replete eggs per day. Sterol synthesis requires molecular oxygen for squalene epoxidation, yet oxygen is scarce in the intestinal folds the worms inhabit. Ascaris has an oxygen-avid hemoglobin in the perienteric fluid that bathes its reproductive organs. Purified hemoglobin contained tightly bound squalene and functioned as an NADPH-dependent, ferrihemoprotein reductase. All components of the squalene epoxidation reaction--squalene, oxygen, NADPH, and NADPH-dependent reductase--are assembled on the hemoglobin. This molecule may thus function in sterol biosynthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sherman, D R -- Guinn, B -- Perdok, M M -- Goldberg, D E -- AM-20579/AM/NIADDK NIH HHS/ -- RR-00954/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 18;258(5090):1930-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Washington University School of Medicine, St. Louis, MO.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1470914" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ascaris/*metabolism ; Hemoglobins/*metabolism ; Kinetics ; Mass Spectrometry ; NADPH-Ferrihemoprotein Reductase/metabolism ; Oxyhemoglobins/*metabolism ; Squalene/metabolism ; Sterols/*biosynthesis/isolation & purification
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  • 94
    Publication Date: 1992-01-03
    Description: Time-correlated single-photon counting of intercalated ethidium bromide was used to measure the torsion constants of positively supercoiled, relaxed, and negatively supercoiled pBR322 DNA, which range in superhelix density from +0.042 to -0.123. DNA behaves as coupled, nonlinear torsional pendulums under superhelical stress, and the anharmonic term in the Hamiltonian is approximately 15 percent for root-mean-square fluctuations in twist at room temperature. At the level of secondary structure, positively supercoiled DNA is significantly more flexible than negatively supercoiled DNA. These results exclude certain models that account for differential binding affinity of proteins to positively and negatively supercoiled DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selvin, P R -- Cook, D N -- Pon, N G -- Bauer, W R -- Klein, M P -- Hearst, J E -- FD 8R1 GM 41911A-03-NF-03/92/FD/FDA HHS/ -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):82-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of California, Berkeley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553534" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Superhelical/*chemistry ; Ethidium ; Intercalating Agents ; Kinetics ; Mathematics ; Models, Theoretical ; Nucleic Acid Conformation ; *Plasmids ; Spectrometry, Fluorescence ; Stress, Mechanical ; Thermodynamics
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  • 95
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-03
    Description: Lymphocytes must proliferate and differentiate in response to low concentrations of a vast array of antigens. The requirements of broad specificity and sensitivity conflict because the former is met by low-affinity antigen receptors, which precludes achieving the latter with high-affinity receptors. Coligation of the membrane protein CD19 with the antigen receptor of B lymphocytes decreased the threshold for antigen receptor-dependent stimulation by two orders of magnitude. B lymphocytes proliferated when approximately 100 antigen receptors per cell, 0.03 percent of the total, were coligated with CD19. The B cell resolves its dilemma by having an accessory protein that enables activation when few antigen receptors are occupied.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carter, R H -- Fearon, D T -- AI-22833/AI/NIAID NIH HHS/ -- AI-28191/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 3;256(5053):105-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373518" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antigens, CD/genetics/*immunology ; Antigens, CD19 ; Antigens, Differentiation, B-Lymphocyte/genetics/*immunology ; B-Lymphocytes/*immunology ; Cell Line ; Cells, Cultured ; DNA Replication ; Humans ; Kinetics ; L Cells (Cell Line) ; *Lymphocyte Activation ; Mice ; Receptors, Antigen, B-Cell/*immunology ; Recombinant Proteins/immunology ; Thymidine/metabolism
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  • 96
    Publication Date: 1992-08-14
    Description: The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line. Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS cells transfected with recombinant p70 S6 kinase completely inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Price, D J -- Grove, J R -- Calvo, V -- Avruch, J -- Bierer, B E -- P01 CA39542/CA/NCI NIH HHS/ -- R01 DK17776/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):973-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Unit, Massachusetts General Hospital, Boston.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinases ; Cell Line ; Chromatography, Ion Exchange ; Cyclosporine/pharmacology ; Immunosuppressive Agents/*pharmacology ; Insulin/pharmacology ; Kinetics ; Liver Neoplasms, Experimental ; Polyenes/*pharmacology ; *Protein Kinase Inhibitors ; Protein Kinases/genetics/isolation & purification/*metabolism ; Recombinant Proteins/antagonists & inhibitors/isolation & purification ; Ribosomal Protein S6 Kinases ; Ribosomes/enzymology ; Sirolimus ; Tacrolimus/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 1992-12-11
    Description: Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes. In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kitajima, I -- Shinohara, T -- Bilakovics, J -- Brown, D A -- Xu, X -- Nerenberg, M -- CA50234/CA/NCI NIH HHS/ -- MH47680/MH/NIMH NIH HHS/ -- NS01330/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1792-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1299224" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Base Sequence ; Cell Division/drug effects ; Cell Line ; Cell Transformation, Neoplastic ; Fibrosarcoma/*drug therapy/pathology ; *Genes, pX ; Human T-lymphotropic virus 1/*genetics ; Humans ; Kinetics ; Lymphocytes ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; NF-kappa B/*antagonists & inhibitors/genetics ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense/*pharmacology/*therapeutic use
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-31
    Description: Subdomain-size proteolytic fragments of Escherichia coli trp repressor have been produced that assemble in defined order to regenerate fully native dimers. By characterization of the secondary and tertiary structures of isolated and recombined fragments, the structure of assembly intermediates can be correlated with the kinetic folding pathway of the intact repressor deduced from spectroscopic measurement of folding rates. The nativelike structure of these intermediates provides further evidence that protein folding pathways reflect the stabilities of secondary structural units and assemblies found in the native state. The proteolytic method should be generally useful in adding structural detail to spectroscopically determined folding mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tasayco, M L -- Carey, J -- GM43558/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 31;255(5044):594-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chemistry Department, Princeton University, NJ 08544.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1736361" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry ; Circular Dichroism ; Escherichia coli/metabolism ; Kinetics ; Macromolecular Substances ; Magnetic Resonance Spectroscopy/methods ; Models, Structural ; Molecular Sequence Data ; Peptide Fragments/chemistry ; Protein Conformation ; Repressor Proteins/*chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 1992-08-14
    Description: The peptide binding cleft of the class I human histocompatibility antigen, HLA-A2, contains conserved amino acid residues clustered in the two ends of the cleft in pockets A and F as well as polymorphic residues. The function of two conserved tyrosines in the A pocket was investigated by mutating them to phenylalanines and of a conserved tyrosine and threonine in the F pocket by mutating them to phenylalanine and valine, respectively. Presentation of influenza virus peptides and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The magnitude of the reduction seen by the mutation of the two tyrosines in the A pocket suggests that hydrogen bonds involving them have a critical function in the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all bound peptide nonamers. In contrast, the mutations in the F pocket had no effect on CTL recognition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Latron, F -- Pazmany, L -- Morrison, J -- Moots, R -- Saper, M A -- McMichael, A -- Strominger, J L -- AI 20182/AI/NIAID NIH HHS/ -- CA 47554/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):964-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Binding Sites ; Cell Line ; Cloning, Molecular ; Epitopes/immunology/metabolism ; HLA-A2 Antigen/chemistry/genetics/*metabolism ; Influenza A virus ; Kinetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Oligopeptides/immunology/*metabolism ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection ; Viral Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1992-07-31
    Description: gamma-Aminobutyric acidA (GABAA) receptors are ligand-gated ion channels that mediate inhibitory synaptic transmission in the central nervous system. The role of protein phosphorylation in the modulation of GABAA receptor function was examined with cells transiently transfected with GABAA receptor subunits. GABAA receptors consisting of the alpha 1 and beta 1 or the alpha 1, beta 1, and gamma 2 subunits were directly phosphorylated on the beta 1 subunit by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA). The phosphorylation decreased the amplitude of the GABA response of both receptor types and the extent of rapid desensitization of the GABAA receptor that consisted of the alpha 1 and beta 1 subunits. Site-specific mutagenesis of the serine residue phosphorylated by PKA completely eliminated the PKA phosphorylation and modulation of the GABAA receptor. In primary embryonic rat neuronal cell cultures, a similar regulation of GABAA receptors by PKA was observed. These results demonstrate that the GABAA receptor is directly modulated by protein phosphorylation and suggest that neurotransmitters or neuropeptides that regulate intracellular cAMP levels may modulate the responses of neurons to GABA and consequently have profound effects on synaptic excitability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moss, S J -- Smart, T G -- Blackstone, C D -- Huganir, R L -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1992 Jul 31;257(5070):661-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Colforsin/pharmacology ; Cyclic AMP/*pharmacology ; Electric Conductivity ; Immunosorbent Techniques ; Kinetics ; Mice ; Mutagenesis, Site-Directed ; Neurons/drug effects/physiology ; Peptide Mapping ; Phosphorylation ; Protein Kinases/*metabolism ; Rats ; Receptors, GABA-A/genetics/*physiology ; Recombinant Proteins/physiology ; Transfection ; Zinc/pharmacology ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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