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  • Cell Line  (70)
  • American Association for the Advancement of Science (AAAS)  (70)
  • American Meteorological Society
  • 1995-1999  (70)
  • 1990-1994
  • 1996  (70)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (70)
  • American Meteorological Society
Years
  • 1995-1999  (70)
  • 1990-1994
Year
  • 1
    Publication Date: 1996-07-19
    Description: Signaling molecules are essential for vertebrate embryonic development. Here, two Xenopus homologs of the Drosophila gene fringe, lunatic Fringe (lFng) and radical Fringe (rFng), were identified and the protein product of lFng further characterized. The messenger RNA of lFng is supplied as a maternal message. Its product is a precursor protein consisting of pre-, pro-, and mature regions. The mature lunatic Fringe protein is secreted extracellularly, and it induced mesodermal tissue formation in animal cap assays. These results indicate that secreted lunatic Fringe can induce mesoderm and reveal that the Fringe proteins are a family of vertebrate signaling molecules.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080353/" 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/PMC2080353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J Y -- Wen, L -- Zhang, W J -- Rao, Y -- R01 CA114197/CA/NCI NIH HHS/ -- R01 CA114197-01A2/CA/NCI NIH HHS/ -- R01 EY014576/EY/NEI NIH HHS/ -- R01 EY014576-03/EY/NEI NIH HHS/ -- R01 GM070967/GM/NIGMS NIH HHS/ -- R01 GM070967-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 19;273(5273):355-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662522" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Blastocyst/metabolism ; Cell Line ; Culture Media, Conditioned ; Culture Techniques ; Drosophila Proteins ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; *Embryonic Induction ; *Glycosyltransferases ; Mesoderm/*metabolism ; Molecular Sequence Data ; *N-Acetylglucosaminyltransferases ; Polymerase Chain Reaction ; Protein Processing, Post-Translational ; Proteins/chemistry/genetics/*physiology/secretion ; RNA, Messenger/genetics/metabolism ; *Signal Transduction ; Xenopus/*embryology/genetics ; *Xenopus Proteins
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  • 2
    Publication Date: 1996-03-01
    Description: Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soto-Ramirez, L E -- Renjifo, B -- McLane, M F -- Marlink, R -- O'Hara, C -- Sutthent, R -- Wasi, C -- Vithayasai, P -- Vithayasai, V -- Apichartpiyakul, C -- Auewarakul, P -- Pena Cruz, V -- Chui, D S -- Osathanondh, R -- Mayer, K -- Lee, T H -- Essex, M -- 5 D43 TW0004/TW/FIC NIH HHS/ -- CA 39805/CA/NCI NIH HHS/ -- HL 33774/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Mar 1;271(5253):1291-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard AIDS Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638113" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cells, Cultured ; HIV Core Protein p24/analysis ; HIV Infections/*transmission/virology ; HIV-1/classification/*growth & development/isolation & purification ; Homosexuality, Male ; Humans ; Langerhans Cells/*virology ; Macrophages/virology ; Male ; Monocytes/virology ; *Sexual Behavior ; Sexually Transmitted Diseases, Viral/*transmission/virology ; T-Lymphocytes/virology ; Thailand ; United States ; Virus Replication
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  • 3
    Publication Date: 1996-11-22
    Description: The RAC guanine nucleotide binding proteins regulate multiple biological activities, including actin polymerization, activation of the Jun kinase (JNK) cascade, and cell proliferation. RAC effector loop mutants were identified that separate the ability of RAC to interact with different downstream effectors. One mutant of activated human RAC protein, RACV12H40 (with valine and histidine substituted at position 12 and 40, respectively), was defective in binding to PAK3, a Ste20-related p21-activated kinase (PAK), but bound to POR1, a RAC-binding protein. This mutant failed to stimulate PAK and JNK activity but still induced membrane ruffling and mediated transformation. A second mutant, RACV12L37 (with leucine substituted at position 37), which bound PAK but not POR1, induced JNK activation but was defective in inducing membrane ruffling and transformation. These results indicate that the effects of RAC on the JNK cascade and on actin polymerization and cell proliferation are mediated by distinct effector pathways that diverge at the level of RAC itself.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joneson, T -- McDonough, M -- Bar-Sagi, D -- Van Aelst, L -- CA55360/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Nov 22;274(5291):1374-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8910277" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Actins/*metabolism ; *Adaptor Proteins, Signal Transducing ; Animals ; COS Cells ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Carrier Proteins/metabolism ; *Cell Division ; Cell Line ; Cell Line, Transformed ; Cell Membrane/ultrastructure ; Enzyme Activation ; GTP-Binding Proteins/genetics/metabolism/*physiology ; Humans ; JNK Mitogen-Activated Protein Kinases ; Mice ; *Mitogen-Activated Protein Kinases ; Mutagenesis ; Protein-Serine-Threonine Kinases/metabolism ; Rats ; Transfection ; p21-Activated Kinases ; rac GTP-Binding Proteins
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  • 4
    Publication Date: 1996-06-07
    Description: The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription factors are expressed in the myotome of developing somites and cooperatively activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome. Ectopically expressed mouse Twist (Mtwist) was shown to inhibit myogenesis by blocking DNA binding by MyoD, by titrating E proteins, and by inhibiting trans-activation by MEF2. For inhibition of MEF2, Mtwist required heterodimerization with E proteins and an intact basic domain and carboxyl-terminus. Thus, Mtwist inhibits both families of myogenic regulators and may regulate myotome formation temporally or spatially.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spicer, D B -- Rhee, J -- Cheung, W L -- Lassar, A B -- 5-F32-AR08214-02/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 7;272(5267):1476-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8633239" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors ; Cell Differentiation ; Cell Line ; Creatine Kinase/genetics ; DNA/metabolism ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Drosophila ; Drosophila Proteins ; Helix-Loop-Helix Motifs/*physiology ; Inhibitor of Differentiation Protein 1 ; MEF2 Transcription Factors ; Mice ; Muscle, Skeletal/*cytology/metabolism ; MyoD Protein/metabolism/physiology ; Myogenic Regulatory Factors ; Nuclear Proteins/chemistry/metabolism/*physiology ; *Repressor Proteins ; TCF Transcription Factors ; Transcription Factor 7-Like 1 Protein ; Transcription Factors/*antagonists & ; inhibitors/chemistry/genetics/metabolism/physiology ; Transcriptional Activation ; Transfection ; Twist Transcription Factor
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  • 5
    Publication Date: 1996-02-09
    Description: The RAS guanine nucleotide binding proteins activate multiple signaling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of activated H-RAS (H-RASV12, where V12 indicates valine-12) induces membrane ruffling, mitogen-activated protein (MAP) kinase activation, and stimulation of DNA synthesis. A mutant of activated H-RAS, H-RASV12C40 (where C40 indicates cysteine-40), was identified that was defective for MAP kinase activation and stimulation of DNA synthesis, but retained the ability to induce membrane ruffling. Another mutant of activated H-RAS, H-RASV12S35 (where S35 indicates serine-35), which activates MAP kinase, was defective for stimulation of membrane ruffling and induction of DNA synthesis. Expression of both mutants resulted in a stimulation of DNA synthesis that was comparable to that induced by H-RASV12. These results indicate that membrane ruffling and activation of MAP kinase represent distinct RAS effector pathways and that input from both pathways is required for the mitogenic activity of RAS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joneson, T -- White, M A -- Wigler, M H -- Bar-Sagi, D -- CA 55360/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 9;271(5250):810-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook 11794, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8628998" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cell Division ; Cell Line ; Cell Membrane/*ultrastructure ; DNA/biosynthesis ; Enzyme Activation ; GTP-Binding Proteins/genetics/metabolism ; Microinjections ; Mutation ; Plasmids ; Protein-Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-raf ; Rats ; Signal Transduction ; rac GTP-Binding Proteins ; ras Proteins/genetics/*metabolism
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  • 6
    Publication Date: 1996-05-10
    Description: Transcription factors of the NFAT family are thought to play a major role in regulating the expression of cytokine genes and other inducible genes during the immune response. The role of NFAT1 was investigated by targeted disruption of the NFAT1 gene. Unexpectedly, cells from NFAT1 -/- mice showed increased primary responses to Leishmania major and mounted increased secondary responses to ovalbumin in vitro. In an in vivo model of allergic inflammation, the accumulation of eosinophils and levels of serum immunoglobulin E were increased in NFAT1 -/- mice. These results suggest that NFAT1 exerts a negative regulatory influence on the immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xanthoudakis, S -- Viola, J P -- Shaw, K T -- Luo, C -- Wallace, J D -- Bozza, P T -- Luk, D C -- Curran, T -- Rao, A -- CA42471/CA/NCI NIH HHS/ -- GM46227/GM/NIGMS NIH HHS/ -- P30 CA21765/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 May 10;272(5263):892-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurogenetics Program, Department of CNS Research, Hoffmann-LaRoche, Nutley, NJ 07110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629027" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, Protozoan/immunology ; Cell Line ; Cytokines/biosynthesis ; DNA-Binding Proteins/genetics/*physiology ; Eosinophils/immunology ; Gene Targeting ; Hypersensitivity/*immunology ; *Immunity ; Immunoglobulin E/biosynthesis ; Immunologic Memory ; Leishmania major/immunology ; *Lymphocyte Activation ; Mice ; Molecular Sequence Data ; NFATC Transcription Factors ; *Nuclear Proteins ; Ovalbumin/immunology ; T-Lymphocytes/immunology ; Transcription Factors/genetics/*physiology
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  • 7
    Publication Date: 1996-08-16
    Description: A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xing, J -- Ginty, D D -- Greenberg, M E -- CA43855/CA/NCI NIH HHS/ -- NS34814-01/NS/NINDS NIH HHS/ -- P30-HD18655/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 16;273(5277):959-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8688081" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cyclic AMP Response Element-Binding Protein/*metabolism ; Epidermal Growth Factor/pharmacology ; *Gene Expression Regulation ; Growth Substances/*pharmacology ; Humans ; Molecular Sequence Data ; Nerve Growth Factors/pharmacology ; PC12 Cells ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Rats ; Ribosomal Protein S6 Kinases ; *Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Transcriptional Activation ; Transfection ; Tumor Cells, Cultured ; ras Proteins/metabolism
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  • 8
    Publication Date: 1996-08-09
    Description: STAT proteins (signal transducers and activators of transcription) activate distinct target genes despite having similar DNA binding preferences. The transcriptional specificity of STAT proteins was investigated on natural STAT binding sites near the interferon-gamma gene. These sites are arranged in multiple copies and required cooperative interactions for STAT binding. The conserved amino-terminal domain of STAT proteins was required for cooperative DNA binding, although this domain was not essential for dimerization or binding to a single site. Cooperative binding interactions enabled the STAT proteins to recognize variations of the consensus site. These sites can be specific for the different STAT proteins and may function to direct selective transcriptional activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, X -- Sun, Y L -- Hoey, T -- New York, N.Y. -- Science. 1996 Aug 9;273(5276):794-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8670419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Line ; DNA/*metabolism ; DNA-Binding Proteins/chemistry/immunology/*metabolism ; Interferon-gamma/genetics ; Introns ; Molecular Sequence Data ; Mutation ; Oligodeoxyribonucleotides/metabolism ; Promoter Regions, Genetic ; STAT1 Transcription Factor ; STAT4 Transcription Factor ; Sequence Deletion ; Signal Transduction ; Trans-Activators/chemistry/immunology/*metabolism ; *Transcriptional Activation
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-02-23
    Description: The pleiotropic biological activities of interleukin-1 (IL-1) are mediated by its type I receptor (IL-1RI). When the ligand binds, IL-1RI initiates a signaling cascade that results in the activation of the transcription regulator nuclear factor kappa B (NF-kappa B). A protein kinase designated IRAK (IL-1 receptor-associated kinase) was purified, and its complementary DNA was molecularly cloned. When human embryonic kidney cells (cell line 293) over-expressing IL-1RI or HeLa cells were exposed to IL-1, IRAK rapidly associated with the IL-1RI complex and was phosphorylated. The primary amino acid sequence of IRAK shares similarity with that of Pelle, a protein kinase that is essential for the activation of a NF-kappa B homolog in Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, Z -- Henzel, W J -- Gao, X -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1128-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Tularik, Incorporated, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599092" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cloning, Molecular ; DNA, Complementary/genetics ; Drosophila ; *Drosophila Proteins ; HeLa Cells ; Humans ; Interleukin-1/*metabolism/pharmacology ; Interleukin-1 Receptor-Associated Kinases ; Molecular Sequence Data ; Phosphorylation ; Protein Kinases/chemistry/genetics/isolation & purification/*metabolism ; Protein-Serine-Threonine Kinases/chemistry ; Receptors, Interleukin-1/*metabolism ; Transfection
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  • 10
    Publication Date: 1996-06-21
    Description: ZPR1 is a zinc finger protein that binds to the cytoplasmic tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Deletion analysis demonstrated that this binding interaction is mediated by the zinc fingers of ZPR1 and subdomains X and XI of the EGFR tyrosine kinase. Treatment of mammalian cells with EGF caused decreased binding of ZPR1 to the EGFR and the accumulation of ZPR1 in the nucleus. The effect of EGF to regulate ZPR1 binding is dependent on tyrosine phosphorylation of the EGFR. ZPR1 therefore represents a prototype for a class of molecule that binds to the EGFR and is released from the receptor after activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galcheva-Gargova, Z -- Konstantinov, K N -- Wu, I H -- Klier, F G -- Barrett, T -- Davis, R J -- R01-CA58396/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 21;272(5269):1797-802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8650580" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/chemistry/*metabolism/secretion ; Cell Line ; Cell Nucleus/metabolism ; Cloning, Molecular ; Cytoplasm/metabolism ; Epidermal Growth Factor/pharmacology ; Humans ; Immunoblotting ; Male ; Mice ; Molecular Sequence Data ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Structure, Secondary ; RNA, Messenger/genetics/metabolism ; Receptor, Epidermal Growth Factor/chemistry/*metabolism ; Testis/metabolism ; Type C Phospholipases/metabolism ; Vanadates/pharmacology ; *Zinc Fingers ; src Homology Domains
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallagher, R B -- New York, N.Y. -- Science. 1996 Mar 29;271(5257):1825.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596949" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Bacterial Proteins/*metabolism ; Cadherins/*metabolism ; Cell Line ; Fibroblasts/microbiology ; Listeria monocytogenes/*metabolism/ultrastructure ; *Phagocytosis
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  • 12
    Publication Date: 1996-02-02
    Description: Rho, a Ras-like small guanosine triphosphatase, has been implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid (LPA) to form stress fibers and focal contacts. The form of RhoA bound to guanosine triphosphate directly bound to and activated a serine-threonine kinase, protein kinase N (PKN). Activated RhoA formed a complex with PKN and activated it in COS-7 cells. PKN was phosphorylated in Swiss 3T3 cells stimulated with LPA, and this phosphorylation was blocked by treatment of cells with botulinum C3 exoenzyme. Activation of Rho may be linked directly to a serine-threonine kinase pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amano, M -- Mukai, H -- Ono, Y -- Chihara, K -- Matsui, T -- Hamajima, Y -- Okawa, K -- Iwamatsu, A -- Kaibuchi, K -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):648-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571127" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; ADP Ribose Transferases/pharmacology ; Amino Acid Sequence ; Animals ; *Botulinum Toxins ; Cell Line ; Chromatography, Affinity ; Enzyme Activation ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; Guanosine Triphosphate/metabolism ; Lysophospholipids/pharmacology ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Kinase C/*metabolism ; Recombinant Fusion Proteins/metabolism ; rhoA GTP-Binding Protein
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-06-28
    Description: Activated epidermal growth factor (EGF) receptors induce the formation of various complexes of intracellular signaling proteins that are mediated by SRC homology 2 (SH2) and SH3 domains. The activated receptors are also rapidly internalized into the endocytotic compartment and degraded in lysosomes. EGF stimulation of canine epithelial cells induced a rapid and transient association of the SH3-SH2-SH3 protein GRB2 with dynamin, a guanosine triphosphatase that regulates endocytosis. Disruption of GRB2 interactions by microinjection of a peptide corresponding to the GRB2 SH2 domain or its phosphopeptide ligand blocked EGF receptor endocytosis; other SH2 domains that bind EGF receptors or antibodies that neutralize RAS did not. Both activation and termination of EGF signaling appear to be regulated by the diverse interactions of GRB2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Z -- Moran, M F -- New York, N.Y. -- Science. 1996 Jun 28;272(5270):1935-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658166" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antibodies, Monoclonal ; Cell Line ; Dogs ; Dynamins ; *Endocytosis/drug effects ; Epidermal Growth Factor/pharmacology ; GRB2 Adaptor Protein ; GTP Phosphohydrolases/metabolism ; Microinjections ; Peptide Fragments/pharmacology ; Proteins/*metabolism ; Receptor, Epidermal Growth Factor/*metabolism ; Receptors, Transferrin/metabolism ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction ; ras Proteins/immunology/physiology ; src Homology Domains/physiology
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Brien, C -- New York, N.Y. -- Science. 1996 Mar 22;271(5256):1672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596927" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 21/*genetics ; Cystatin B ; Cystatins/*genetics ; Cysteine Proteinase Inhibitors/*genetics ; Epilepsies, Myoclonic/*genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; RNA, Messenger/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 1996-02-02
    Description: The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form and regulates cell adhesion and cytokinesis, but how it exerts these actions is unknown. The yeast two-hybrid system was used to clone a complementary DNA for a protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho-binding domain of this protein has 40 percent identity with a putative regulatory domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by this binding both in vitro and in vivo. This study indicates that a serine-threonine protein kinase is a Rho effector and presents an amino acid sequence motif for binding to GTP-Rho that may be shared by a family of Rho target proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watanabe, G -- Saito, Y -- Madaule, P -- Ishizaki, T -- Fujisawa, K -- Morii, N -- Mukai, H -- Ono, Y -- Kakizuka, A -- Narumiya, S -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):645-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571126" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Cell Line ; Cloning, Molecular ; Enzyme Activation ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Membrane Proteins/*metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Kinase C/chemistry/*metabolism ; *Protein-Serine-Threonine Kinases ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics ; Signal Transduction ; ras Proteins ; *rho GTP-Binding Proteins ; rhoA GTP-Binding Protein ; rhoB GTP-Binding Protein
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-01
    Description: The neurotransmitter functions of nitric oxide are dependent on dynamic regulation of its biosynthetic enzyme, neuronal nitric oxide synthase (nNOS). By means of a yeast two-hybrid screen, a 10-kilodalton protein was identified that physically interacts with and inhibits the activity of nNOS. This inhibitor, designated PIN, appears to be one of the most conserved proteins in nature, showing 92 percent amino acid identity with the nematode and rat homologs. Binding of PIN destabilizes the nNOS dimer, a conformation necessary for activity. These results suggest that PIN may regulate numerous biological processes through its effects on nitric oxide synthase activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaffrey, S R -- Snyder, S H -- DA00074/DA/NIDA NIH HHS/ -- GM-07309/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Nov 1;274(5288):774-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8864115" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/chemistry/genetics/*metabolism/pharmacology ; Cell Line ; Cyclic GMP/metabolism ; Dimerization ; *Drosophila Proteins ; Dyneins ; Enzyme Inhibitors/chemistry/*metabolism/pharmacology ; Humans ; Molecular Sequence Data ; Molecular Weight ; Neurons/enzymology ; Nitric Oxide Synthase/*antagonists & inhibitors/metabolism ; Rats ; Recombinant Fusion Proteins/metabolism/pharmacology ; Saccharomyces cerevisiae ; Transfection
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-06-14
    Description: Mitogen-activated protein kinase (MAPK) cascades, termed MAPK modules, channel extracellular signals into specific cellular responses. Chimeric molecules were constructed between p38 and p44 MAPKs, which transduce stress and growth factor signals, respectively. A discrete region of 40 residues located in the amono-terminal p38MAPK lobe directed the specificity of response to extracellular signals, whereas the p44MAPK chimera, expressed in vivo, redirected stress signals into early mitogenic responses, demonstrating the functional independence of these domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunet, A -- Pouyssegur, J -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1652-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre de Biochemie-CNRS, UMR134, Parc Valrose, Faculte des Sciences, Nice, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658140" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anisomycin/pharmacology ; Binding Sites ; Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism ; Cell Division ; Cell Line ; Cricetinae ; Cricetulus ; Enzyme Activation ; Gene Expression Regulation ; Genes, fos ; Growth Substances/metabolism ; Mice ; Mitogen-Activated Protein Kinase 3 ; *Mitogen-Activated Protein Kinases ; Molecular Sequence Data ; Phosphorylation/drug effects ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Ribosomal Protein S6 Kinases ; Signal Transduction ; Sorbitol/pharmacology ; Substrate Specificity ; p38 Mitogen-Activated Protein Kinases
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  • 18
    Publication Date: 1996-12-20
    Description: The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holmes, T C -- Fadool, D A -- Ren, R -- Levitan, I B -- F32 NS009952/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2089-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02254, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953041" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Cloning, Molecular ; Humans ; Kv1.5 Potassium Channel ; Molecular Sequence Data ; Myocardium/chemistry ; Oncogene Protein pp60(v-src)/metabolism ; Patch-Clamp Techniques ; Phosphorylation ; Phosphotyrosine/metabolism ; Potassium Channels/chemistry/*metabolism ; *Potassium Channels, Voltage-Gated ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transfection ; src Homology Domains/*physiology ; src-Family Kinases/chemistry/*metabolism
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  • 19
    Publication Date: 1996-03-29
    Description: The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel regulated by protein kinase A and adenosine triphosphate (ATP). Loss of CFTR-mediated chloride ion conductance from the apical plasma membrane of epithelial cells is a primary physiological lesion in cystic fibrosis. CFTR has also been suggested to function an an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CFTR in intact organs, polarized human lung cell lines, stably transfected mammalian cell lines, or planar lipid bilayers reconstituted with CFTR protein. These findings suggest that ATP permeation through the CFTR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reddy, M M -- Quinton, P M -- Haws, C -- Wine, J J -- Grygorczyk, R -- Tabcharani, J A -- Hanrahan, J W -- Gunderson, K L -- Kopito, R R -- DK43994/DK/NIDDK NIH HHS/ -- DK45913/DK/NIDDK NIH HHS/ -- HL42368/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Mar 29;271(5257):1876-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biomedical Sciences, University of California, Riverside, 92521, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596959" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism ; Animals ; CHO Cells ; Cell Line ; Cell Membrane/metabolism ; Cell Polarity ; Chlorides/metabolism ; Cricetinae ; Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism ; Humans ; Lipid Bilayers/metabolism ; Lung/cytology/metabolism ; Patch-Clamp Techniques ; Recombinant Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-06-14
    Description: As a model for studying the generation of antibody diversity, a gene-targeted mouse was produced that is hemizygous for a rearranged V(D)J segment at the immunoglobulin (Ig) heavy chain locus, the other allele being nonfunctional. The mouse also has no functional kappa light chain allele. The heavy chain, when paired with any lambda light chain, is specific for the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). The primary repertoire of this quasi-monoclonal mouse is monospecific, but somatic hypermutation and secondary rearrangements change the specificity of 20 percent of the antigen receptors on B cells. The serum concentrations of the Ig isotypes are similar to those in nontransgenic littermates, but less than half of the serum IgM binds to NP, and none of the other isotypes do. Thus, neither network interactions nor random activation of a small fraction of the B cell population can account for serum Ig concentrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cascalho, M -- Ma, A -- Lee, S -- Masat, L -- Wabl, M -- 1R01 GM37699/GM/NIGMS NIH HHS/ -- P60 AR20684/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1649-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco 94143-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658139" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*genetics/immunology ; *Antigens, CD ; Antigens, CD43 ; Antigens, CD45/immunology ; B-Lymphocytes/cytology/immunology ; Base Sequence ; Cell Line ; Cloning, Molecular ; Dna ; Flow Cytometry ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Haptens/immunology ; Immunoglobulin Heavy Chains/*genetics/immunology ; Immunoglobulin Isotypes/genetics ; Immunoglobulin J-Chains/genetics ; Immunoglobulin Light Chains/genetics/immunology ; Immunoglobulin Variable Region/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout/genetics/*immunology ; Molecular Sequence Data ; Nitrophenols/immunology ; Phenylacetates ; Recombinant Proteins/genetics/immunology ; Sialoglycoproteins/immunology
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-10-11
    Description: Hedgehog (Hh) proteins comprise a family of secreted signaling molecules essential for patterning a variety of structures in animal embryogenesis. During biosynthesis, Hh undergoes an autocleavage reaction, mediated by its carboxyl-terminal domain, that produces a lipid-modified amino-terminal fragment responsible for all known Hh signaling activity. Here it is reported that cholesterol is the lipophilic moiety covalently attached to the amino-terminal signaling domain during autoprocessing and that the carboxyl-terminal domain acts as an intramolecular cholesterol transferase. This use of cholesterol to modify embryonic signaling proteins may account for some of the effects of perturbed cholesterol biosynthesis on animal development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Porter, J A -- Young, K E -- Beachy, P A -- New York, N.Y. -- Science. 1996 Oct 11;274(5285):255-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8824192" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Cholesterol/*metabolism ; Dithiothreitol/pharmacology ; Drosophila ; *Drosophila Proteins ; *Embryonic Induction ; Embryonic and Fetal Development ; Hedgehog Proteins ; Humans ; Protein Processing, Post-Translational ; Proteins/genetics/*metabolism ; Signal Transduction ; *Trans-Activators
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  • 22
    Publication Date: 1996-07-26
    Description: B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol 1,4,5-trisphosphate receptor (IP3R) and increased amounts of IP3R protein. Immunohistochemical analysis revealed that the augmented receptor population was localized to the plasma membrane. Type 3 IP3R (IP3R3) was selectively increased during apoptosis, with no enhancement of type 1 IP3R (IP3R1). Expression of IP3R3 antisense constructs in S49 T cells blocked dexamethasone-induced apoptosis, whereas IP3R3 sense, IP3R1 sense, or IP3R1 antisense control constructs did not block cell death. Thus, the increases in IP3R3 may be causally related to apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khan, A A -- Soloski, M J -- Sharp, A H -- Schilling, G -- Sabatini, D M -- Li, S H -- Ross, C A -- Snyder, S H -- AI-20922/AI/NIAID NIH HHS/ -- AI-37934/AI/NIAID NIH HHS/ -- MH43040/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):503-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662540" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Apoptosis ; B-Lymphocytes/*cytology/metabolism ; Base Sequence ; Calcium/metabolism ; Calcium Channels/genetics/immunology/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Cells, Cultured ; DNA, Antisense ; Dexamethasone/pharmacology ; Immunoblotting ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; Mice ; Molecular Sequence Data ; Receptors, Cytoplasmic and Nuclear/genetics/immunology/*metabolism ; T-Lymphocytes/*cytology/metabolism ; Transfection ; Tumor Cells, Cultured
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  • 23
    Publication Date: 1996-02-09
    Description: Genetic studies indicated that the Drosophila melanogaster protein REAPER (RPR) controls apoptosis during embryo development. Induction of RPR expression in Drosophila Schneider cells rapidly stimulated apoptosis. RPR-mediated apoptosis was blocked by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), which suggests that an interleukin-1 beta converting enzyme (ICE)-like protease is required for RPR function. RPR-induced apoptosis was associated with increased ceramide production that was also blocked by Z-VAD-fmk, which suggests that ceramide generation requires an ICE-like protease as well. Thus, the intracellular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor necrosis factor receptor type 1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pronk, G J -- Ramer, K -- Amiri, P -- Williams, L T -- New York, N.Y. -- Science. 1996 Feb 9;271(5250):808-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chiron Corporation, Emeryville, CA 94608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8628997" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Chloromethyl Ketones/pharmacology ; Amino Acid Sequence ; Animals ; *Apoptosis/drug effects ; Caspase 1 ; Cell Line ; Ceramides/*metabolism/pharmacology ; Copper/pharmacology ; Copper Sulfate ; Cysteine Endopeptidases/*metabolism ; *Drosophila Proteins ; Drosophila melanogaster/*cytology/embryology/genetics/metabolism ; Enzyme Activation ; Gene Expression ; Molecular Sequence Data ; Peptides/genetics/*physiology ; Protease Inhibitors/pharmacology ; Signal Transduction ; Transfection
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  • 24
    Publication Date: 1996-06-28
    Description: Homozygous weaver mice are profoundly ataxic because of the loss of granule cell neurons during cerebellar development. This granule cell loss appears to be caused by a genetic defect in the pore region (Gly156--〉Ser) of the heterotrimeric guanine nucleotide-binding protein (G protein)-gated inwardly rectifying potassium (K+) channel subunit (GIRK2). A related subunit, GIRK1, associates with GIRK2 to constitute a neuronal G protein-gated inward rectifier K+ channel. The weaver allele of the GIRK2 subunit (wvGIRK2) caused loss of K+ selectivity when expressed either as wvGIRK2 homomultimers or as GIRK1-wvGIRK2 heteromultimers. The mutation also let to loss of sensitivity to G protein betagamma dimers. Expression of wvGIRK2 subunits let to increased cell death, presumably as a result of basal nonselective channel opening.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Navarro, B -- Kennedy, M E -- Velimirovic, B -- Bhat, D -- Peterson, A S -- Clapham, D E -- New York, N.Y. -- Science. 1996 Jun 28;272(5270):1950-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658170" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antisense Elements (Genetics) ; CHO Cells ; Cell Death ; Cell Line ; Cerebellum/cytology/*metabolism ; Cricetinae ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; GTP-Binding Proteins/*physiology ; Membrane Potentials ; Mice ; Mice, Neurologic Mutants ; Molecular Sequence Data ; Neurons/cytology/metabolism ; Oocytes/cytology ; Patch-Clamp Techniques ; Point Mutation ; Potassium Channels/genetics/*metabolism ; *Potassium Channels, Inwardly Rectifying ; Transfection
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-03
    Description: During mouse embryogenesis the production of "primitive" erythrocytes (EryP) precedes the production of "definitive" erythrocytes (EryD) in parallel with the transition of the hematopoietic site from the yolk sac to the fetal liver. On a macrophage colony-stimulating factor-deficient stromal cell line OP9, mouse embryonic stem cells were shown to give rise to EryP and EryD sequentially with a time course similar to that seen in murine ontogeny. Studies of the different growth factor requirements and limiting dilution analysis of precursor frequencies indicate that most EryP and EryD probably developed from different precursors by way of distinct differentiation pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakano, T -- Kodama, H -- Honjo, T -- New York, N.Y. -- Science. 1996 May 3;272(5262):722-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614833" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Division ; Cell Line ; Cell Lineage ; Cell Separation ; Cells, Cultured ; Coculture Techniques ; Erythroid Precursor Cells/*cytology ; *Erythropoiesis ; Erythropoietin/pharmacology ; Kinetics ; Mice ; Signal Transduction ; Stem Cell Factor/physiology
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-07-05
    Description: The requirements for T cell activation have been reported to vary widely depending on the state of the T cell, the type of antigen-presenting cell, and the nature of the T cell receptor (TCR) ligand. A unitary requirement for T cell responses was revealed by measurement of the number of triggered TCRs. Irrespective of the nature of the triggering ligand, T cells "counted" the number of triggered TCRs and responded when a threshold of approximately 8000 TCRs was reached. The capacity to reach the activation threshold was severely compromised by a reduction in the number of TCRs. Costimulatory signals lowered the activation threshold to approximately 1500 TCRs, thus making T cells more sensitive to antigenic stimulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viola, A -- Lanzavecchia, A -- New York, N.Y. -- Science. 1996 Jul 5;273(5271):104-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Basel Institute for Immunology, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658175" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/immunology ; Antigen-Presenting Cells/immunology ; Antigens, CD3/immunology ; Antigens, CD80/immunology ; *Bacterial Toxins ; Cell Line ; Clone Cells ; Down-Regulation ; Enterotoxins/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Interferon-gamma/biosynthesis ; *Lymphocyte Activation ; Peptides/immunology ; Receptors, Antigen, T-Cell/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Superantigens/immunology ; T-Lymphocytes/*immunology
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-01-26
    Description: Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a functional selection strategy. ALG-2 codes for a Ca(2+)-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis. These findings suggest that ALG-2 may mediate Ca(2+)-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vito, P -- Lacana, E -- D'Adamio, L -- New York, N.Y. -- Science. 1996 Jan 26;271(5248):521-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉T Cell Molecular Biology Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8560270" target="_blank"〉PubMed〈/a〉
    Keywords: Alkaloids/pharmacology ; Alzheimer Disease/*genetics ; Amino Acid Sequence ; Animals ; Antigens, CD95/metabolism ; *Apoptosis/drug effects ; Apoptosis Regulatory Proteins ; Calcium/metabolism ; Calcium-Binding Proteins/chemistry/genetics/*physiology ; Cell Line ; Cloning, Molecular ; DNA, Complementary ; Dactinomycin/pharmacology ; Dexamethasone/pharmacology ; Fas Ligand Protein ; Hybridomas ; Interleukin-2/metabolism ; Membrane Glycoproteins/metabolism ; Membrane Proteins/chemistry/genetics/*physiology ; Mice ; Molecular Sequence Data ; Presenilin-2 ; Receptors, Antigen, T-Cell/physiology ; Signal Transduction ; Staurosporine ; T-Lymphocytes ; Transfection ; Up-Regulation
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  • 28
    Publication Date: 1996-06-07
    Description: The adenovirus E4orf6 protein is shown here to interact with the cellular tumor suppressor protein p53 and to block p53-mediated transcriptional activation. The adenovirus protein inhibited the ability of p53 to bind to human TAFII31, a component of transcription factor IID (TFIID). Earlier work demonstrated that the interaction of p53 with TAFII31 involves a sequence near the NH2-terminus of p53, whereas the E4orf6-p53 interaction occurs within amino acids 318 to 360 of p53. Thus, the E4orf6 protein interacts at a site on p53 distinct from the domain that binds to TAFII31 but nevertheless inhibits the p53-TAFII31 interaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dobner, T -- Horikoshi, N -- Rubenwolf, S -- Shenk, T -- New York, N.Y. -- Science. 1996 Jun 7;272(5267):1470-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Medizinische Mikrobiologie und Hygiene, Universitat Regensburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8633237" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/physiology ; Adenovirus E4 Proteins/immunology/*metabolism ; Cell Line ; DNA/metabolism ; Genes, p53 ; HeLa Cells ; Humans ; Immunoblotting ; Recombinant Fusion Proteins/metabolism ; *TATA-Binding Protein Associated Factors ; Trans-Activators/*metabolism ; *Transcription Factor TFIID ; *Transcriptional Activation ; Transfection ; Tumor Suppressor Protein p53/chemistry/*metabolism
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  • 29
    Publication Date: 1996-08-30
    Description: The immediate-early transcription factor NGFI-A (also called Egr-1, zif/268, or Krox-24) is thought to couple extracellular signals to changes in gene expression. Although activins and inhibins regulate follicle-stimulating hormone (FSH) synthesis, no factor has been identified that exclusively regulates luteinizing hormone (LH) synthesis. An analysis of NGFI-A-deficient mice derived from embryonic stem cells demonstrated female infertility that was secondary to LH-beta deficiency. Ovariectomy led to increased amounts of FSH-beta but not LH-beta messenger RNA, which suggested a pituitary defect. A conserved, canonical NGFI-A site in the LH-beta promoter was required for synergistic activation by NGFI-A and steroidogenic factor-1 (SF-1). NGFI-A apparently influences female reproductive capacity through its regulation of LH-beta transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, S L -- Sadovsky, Y -- Swirnoff, A H -- Polish, J A -- Goda, P -- Gavrilina, G -- Milbrandt, J -- CA53524/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 30;273(5279):1219-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8703054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; DNA-Binding Proteins/*genetics ; Early Growth Response Protein 1 ; Female ; Follicle Stimulating Hormone/genetics ; Follicle Stimulating Hormone, beta Subunit ; Fushi Tarazu Transcription Factors ; *Gene Expression Regulation ; Gene Targeting ; Gonadotropins/pharmacology ; Homeodomain Proteins ; *Immediate-Early Proteins ; Infertility, Female/*genetics ; Luteinizing Hormone/analysis/*deficiency/*genetics ; Male ; Mice ; Molecular Sequence Data ; Ovary/drug effects/physiology ; Pituitary Gland/metabolism ; Promoter Regions, Genetic ; Receptors, Cytoplasmic and Nuclear ; Steroidogenic Factor 1 ; Transcription Factors/*genetics ; Transfection ; Uterus/drug effects ; Zinc Fingers
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  • 30
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-29
    Description: Cell cycle phase transitions in eukaryotic cells are driven by regulation of the activity of protein kinases known as cyclin-dependent kinases (Cdks). A broad spectrum of Cdk-inhibitory activity associated with a 28-kilodalton protein (p28lck1) was induced in cells treated with the drug lovastatin or upon density-mediated growth arrest and was periodic in the cell cycle, with peak activity in G1. The p28lck1 protein was shown to be identical to p27Kip1, and the periodic or induced inhibitory activity resulted from a periodic accumulation of the protein. Variations in the amount of p27 protein occurred, whereas the abundance of the p27 messenger RNA remained unchanged. In every instance investigated, the posttranscriptional alteration of p27 protein levels was achieved in part by a mechanism of translational control, although in density-arrested fibroblasts and thymidine-arrested HeLa cells the half-life of the protein was also changed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hengst, L -- Reed, S I -- GM46006/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Mar 29;271(5257):1861-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596954" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Cell Cycle ; *Cell Cycle Proteins ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclin-Dependent Kinases/*antagonists & inhibitors ; Enzyme Inhibitors/metabolism ; G1 Phase ; Half-Life ; HeLa Cells ; Humans ; Lovastatin/pharmacology ; Microtubule-Associated Proteins/*biosynthesis/genetics/metabolism ; Molecular Sequence Data ; Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; S Phase ; Tumor Cells, Cultured ; *Tumor Suppressor Proteins
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  • 31
    Publication Date: 1996-11-29
    Description: Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lesch, K P -- Bengel, D -- Heils, A -- Sabol, S Z -- Greenberg, B D -- Petri, S -- Benjamin, J -- Muller, C R -- Hamer, D H -- Murphy, D L -- New York, N.Y. -- Science. 1996 Nov 29;274(5292):1527-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of Wurzburg, Fuchsleinstrasse 15, 97080 Wurzburg, Germany. kplesch@rzbox.uni-wuerzburg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8929413" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Alleles ; Anxiety Disorders/*genetics ; Carrier Proteins/*genetics ; Cell Line ; Female ; Genetic Markers ; Genotype ; Humans ; Male ; Membrane Glycoproteins/*genetics ; *Membrane Transport Proteins ; Middle Aged ; *Nerve Tissue Proteins ; Neurotic Disorders/*genetics ; Nuclear Family ; Personality Tests ; Phenotype ; *Polymorphism, Genetic ; *Promoter Regions, Genetic ; Serotonin/*metabolism ; Serotonin Plasma Membrane Transport Proteins ; Transfection
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  • 32
    Publication Date: 1996-02-09
    Description: When mammalian cells were treated with triplex-forming oligonucleotides of sufficient binding affinity, mutations were specifically induced in a simian virus 40 vector contained within the cells. Triplex-induced mutagenesis was not detected in xeroderma pigmentosum group A cells nor in Cockayne's syndrome group B cells, indicating a requirement for excision repair and for transcription-coupled repair, respectively, in the process. Triplex formation was also found to stimulate DNA repair synthesis in human cell extracts, in a pattern correlating with the inhibition of transcription in such extracts. These findings may have implications for therapeutic applications of triplex DNA and raise the possibility that naturally occurring triple helices are a source of genetic instability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, G -- Seidman, M M -- Glazer, P M -- CA64186/CA/NCI NIH HHS/ -- ES05775/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 9;271(5250):802-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8628995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; DNA/biosynthesis/*metabolism ; *DNA Repair ; Genetic Vectors ; Haplorhini ; HeLa Cells ; Humans ; Molecular Sequence Data ; *Mutagenesis ; Oligodeoxyribonucleotides/*metabolism ; Point Mutation ; Sequence Deletion ; *Transcription, Genetic ; Transfection
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  • 33
    Publication Date: 1996-10-25
    Description: The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schuler, G D -- Boguski, M S -- Stewart, E A -- Stein, L D -- Gyapay, G -- Rice, K -- White, R E -- Rodriguez-Tome, P -- Aggarwal, A -- Bajorek, E -- Bentolila, S -- Birren, B B -- Butler, A -- Castle, A B -- Chiannilkulchai, N -- Chu, A -- Clee, C -- Cowles, S -- Day, P J -- Dibling, T -- Drouot, N -- Dunham, I -- Duprat, S -- East, C -- Edwards, C -- Fan, J B -- Fang, N -- Fizames, C -- Garrett, C -- Green, L -- Hadley, D -- Harris, M -- Harrison, P -- Brady, S -- Hicks, A -- Holloway, E -- Hui, L -- Hussain, S -- Louis-Dit-Sully, C -- Ma, J -- MacGilvery, A -- Mader, C -- Maratukulam, A -- Matise, T C -- McKusick, K B -- Morissette, J -- Mungall, A -- Muselet, D -- Nusbaum, H C -- Page, D C -- Peck, A -- Perkins, S -- Piercy, M -- Qin, F -- Quackenbush, J -- Ranby, S -- Reif, T -- Rozen, S -- Sanders, C -- She, X -- Silva, J -- Slonim, D K -- Soderlund, C -- Sun, W L -- Tabar, P -- Thangarajah, T -- Vega-Czarny, N -- Vollrath, D -- Voyticky, S -- Wilmer, T -- Wu, X -- Adams, M D -- Auffray, C -- Walter, N A -- Brandon, R -- Dehejia, A -- Goodfellow, P N -- Houlgatte, R -- Hudson, J R Jr -- Ide, S E -- Iorio, K R -- Lee, W Y -- Seki, N -- Nagase, T -- Ishikawa, K -- Nomura, N -- Phillips, C -- Polymeropoulos, M H -- Sandusky, M -- Schmitt, K -- Berry, R -- Swanson, K -- Torres, R -- Venter, J C -- Sikela, J M -- Beckmann, J S -- Weissenbach, J -- Myers, R M -- Cox, D R -- James, M R -- Bentley, D -- Deloukas, P -- Lander, E S -- Hudson, T J -- HG00098/HG/NHGRI NIH HHS/ -- HG00206/HG/NHGRI NIH HHS/ -- HG00835/HG/NHGRI NIH HHS/ -- Wellcome Trust/United Kingdom -- etc. -- New York, N.Y. -- Science. 1996 Oct 25;274(5287):540-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8849440" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; *Chromosome Mapping ; Chromosomes, Artificial, Yeast ; Computer Communication Networks ; DNA, Complementary/genetics ; Databases, Factual ; Gene Expression ; Genetic Markers ; *Genome, Human ; *Human Genome Project ; Humans ; Multigene Family ; RNA, Messenger/genetics ; Sequence Homology, Nucleic Acid ; Sequence Tagged Sites
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  • 34
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-07-19
    Description: Proliferating murine C2C12 myoblasts can undergo either terminal differentiation or programmed cell death under conditions of mitogen deprivation. Unlike myoblasts, differentiated myotubes were resistant to apoptosis. During myogenesis the appearance of the apoptosis-resistant phenotype was correlated with the induction of the cyclin-dependent kinase (Cdk) inhibitor p21(CIP1) but not with the appearance of myogenin, a marker expressed earlier in differentiation. Forced expression of the Cdk inhibitors p21(CIP1) or p16(INK4A) blocked apoptosis during myocyte differentiation. These data indicate that induction of Cdk inhibitors may serve to protect differentiating myocytes from programmed cell death as well as play a role in establishing the postmitotic state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641673/" 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/PMC3641673/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, J -- Walsh, K -- AR40197/AR/NIAMS NIH HHS/ -- HL50692/HL/NHLBI NIH HHS/ -- R01 AG015052/AG/NIA NIH HHS/ -- R01 AR040197/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 19;273(5273):359-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cardiovascular Research, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, MA 02135, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Carrier Proteins/biosynthesis/genetics/*physiology ; *Cell Differentiation ; Cell Line ; Culture Media ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinases/*antagonists & inhibitors ; Cyclins/biosynthesis/genetics/*physiology ; Enzyme Inhibitors/metabolism ; Mice ; Muscles/*cytology/metabolism ; Myogenin/biosynthesis ; Phenotype ; Transfection
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  • 35
    Publication Date: 1996-10-04
    Description: Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID). Although several genetic causes are known for B+ SCID, the etiology of B- SCID has not been defined. Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both. This mutation resulted in a functional inability to form antigen receptors through genetic recombination and links a defect in one of the site-specific recombination systems to a human disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwarz, K -- Gauss, G H -- Ludwig, L -- Pannicke, U -- Li, Z -- Lindner, D -- Friedrich, W -- Seger, R A -- Hansen-Hagge, T E -- Desiderio, S -- Lieber, M R -- Bartram, C R -- New York, N.Y. -- Science. 1996 Oct 4;274(5284):97-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Molecular Biology, University of Ulm, D-89070 Ulm, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8810255" target="_blank"〉PubMed〈/a〉
    Keywords: B-Lymphocytes/immunology ; Cell Line ; Consanguinity ; *DNA-Binding Proteins ; Female ; Genes, Immunoglobulin ; Genes, Recessive ; *Homeodomain Proteins ; Humans ; Immunophenotyping ; Male ; Mutation ; Nuclear Proteins ; Polymorphism, Single-Stranded Conformational ; Proteins/*genetics ; Receptors, Antigen, T-Cell/genetics ; Recombination, Genetic ; Sequence Deletion ; Severe Combined Immunodeficiency/*genetics/immunology ; Transfection
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  • 36
    Publication Date: 1996-02-23
    Description: The alpha subunit of p21(RAS) farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-beta (TGF-beta) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-beta type l receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-beta type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-beta and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21(RAS).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, T -- Danielson, P D -- Li, B Y -- Shah, P C -- Kim, S D -- Donahoe, P K -- HD28138/HD/NICHD NIH HHS/ -- R01 HD3081/HD/NICHD NIH HHS/ -- R01 HD32112/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1120-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599089" target="_blank"〉PubMed〈/a〉
    Keywords: Activin Receptors ; *Activin Receptors, Type I ; Activins ; *Alkyl and Aryl Transferases ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Humans ; Inhibins/*metabolism ; Ligands ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Receptors, Growth Factor/metabolism ; Receptors, Transforming Growth Factor beta/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; Transferases/*metabolism ; Transforming Growth Factor beta/*metabolism
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  • 37
    Publication Date: 1996-12-13
    Description: The induction of cytokine gene transcription is mediated in part by the nuclear factor of activated T cells (NF-AT). Factors involved in the mechanisms of NF-AT-mediated transcription are not well understood. A nuclear factor that interacted with the Rel homology domain (RHD) of NF-ATp was identified with the use of a two-hybrid interaction trap. Designated NIP45 (NF-AT interacting protein), it has minimal similarity to any known genes. Transcripts encoding this factor were enriched in lymphoid tissues and testes. NIP45 synergized with NF-ATp and the proto-oncogene c-Maf to activate the interleukin-4 (IL-4) cytokine promoter; transient overexpression of NIP45 with NF-ATp and c-maf in B lymphoma cells induced measurable endogenous IL-4 protein production. The identification of NIP45 advances our understanding of gene activation of cytokines, critical mediators of the immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hodge, M R -- Chun, H J -- Rengarajan, J -- Alt, A -- Lieberson, R -- Glimcher, L H -- AI37833/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 13;274(5294):1903-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Harvard School of Public Health and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8943202" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cloning, Molecular ; DNA-Binding Proteins/*metabolism ; Genes, Reporter ; Humans ; Interleukin-4/*genetics ; *Intracellular Signaling Peptides and Proteins ; Male ; Molecular Sequence Data ; NFATC Transcription Factors ; Nuclear Proteins/chemistry/genetics/*metabolism ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Spleen/metabolism ; Testis/metabolism ; Thymus Gland/metabolism ; Transcription Factors/*metabolism ; *Transcriptional Activation ; Transfection ; Tumor Cells, Cultured
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  • 38
    Publication Date: 1996-08-16
    Description: Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howard, A D -- Feighner, S D -- Cully, D F -- Arena, J P -- Liberator, P A -- Rosenblum, C I -- Hamelin, M -- Hreniuk, D L -- Palyha, O C -- Anderson, J -- Paress, P S -- Diaz, C -- Chou, M -- Liu, K K -- McKee, K K -- Pong, S S -- Chaung, L Y -- Elbrecht, A -- Dashkevicz, M -- Heavens, R -- Rigby, M -- Sirinathsinghji, D J -- Dean, D C -- Melillo, D G -- Patchett, A A -- Nargund, R -- Griffin, P R -- DeMartino, J A -- Gupta, S K -- Schaeffer, J M -- Smith, R G -- Van der Ploeg, L H -- New York, N.Y. -- Science. 1996 Aug 16;273(5277):974-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Research Laboratories, Rahway, NJ 07065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8688086" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Codon ; DNA, Complementary/genetics ; GTP-Binding Proteins/metabolism ; Growth Hormone/*secretion ; Hormones/*metabolism ; Humans ; Hypothalamus, Middle/chemistry ; Indoles/*metabolism/pharmacology ; Macaca mulatta ; Molecular Sequence Data ; Oligopeptides/*metabolism ; Pituitary Gland/chemistry ; RNA, Complementary/genetics ; Rats ; Receptors, Cell Surface/analysis/chemistry/genetics/*metabolism ; *Receptors, G-Protein-Coupled ; Receptors, Ghrelin ; Spiro Compounds/*metabolism/pharmacology ; Swine
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  • 39
    Publication Date: 1996-12-20
    Description: Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, E -- Kim, J B -- Sarraf, P -- Spiegelman, B M -- R37DK31405/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2100-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953045" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Adipocytes/*cytology/metabolism ; Animals ; Blood ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism ; Cell Differentiation ; Cell Line ; Enzyme Inhibitors/pharmacology ; Epidermal Growth Factor/pharmacology ; Flavonoids/pharmacology ; Insulin/pharmacology ; Ligands ; Mice ; Mitogens/pharmacology ; Mutation ; Phosphorylation ; Rats ; Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic/drug effects ; Transfection
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  • 40
    Publication Date: 1996-01-26
    Description: A subset of individuals with familial amyotrophic lateral sclerosis (FALS) possesses dominantly inherited mutations in the gene that encodes copper-zinc superoxide dismutase (CuZnSOD). A4V and G93A, two of the mutant enzymes associated with FALS, were shown to catalyze the oxidation of a model substrate (spin trap 5,5'-dimethyl-1-pyrroline N-oxide) by hydrogen peroxide at a higher rate than that seen with the wild-type enzyme. Catalysis of this reaction by A4V and G93A was more sensitive to inhibition by the copper chelators diethyldithiocarbamate and penicillamine than was catalysis by wild-type CuZnSOD. The same two chelators reversed the apoptosis-inducing effect of mutant enzymes expressed in a neural cell line. These results suggest that oxidative reactions catalyzed by mutant CuZnSOD enzymes initiate the neuropathologic changes in FALS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiedau-Pazos, M -- Goto, J J -- Rabizadeh, S -- Gralla, E B -- Roe, J A -- Lee, M K -- Valentine, J S -- Bredesen, D E -- AG12282/AG/NIA NIH HHS/ -- DK46828/DK/NIDDK NIH HHS/ -- GM28222/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jan 26;271(5248):515-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, Los Angeles 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8560268" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*enzymology/genetics ; Animals ; Apoptosis/drug effects ; Binding Sites ; Catalysis ; Cell Line ; Chelating Agents/pharmacology ; Copper/metabolism ; Cyclic N-Oxides/metabolism ; Ditiocarb/pharmacology ; Humans ; Hydrogen Peroxide/metabolism ; Mutation ; Oxidation-Reduction ; Penicillamine/pharmacology ; Rats ; Superoxide Dismutase/genetics/*metabolism
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  • 41
    Publication Date: 1996-05-10
    Description: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated "fusin," is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and HIV-1 infection. Antibodies to fusin blocked cell fusion and infection with normal CD4-positive human target cells. Fusin messenger RNA levels correlated with HIV-1 permissiveness in diverse human cell types. Fusin acted preferentially for T cell line-tropic isolates, in comparison to its activity with macrophagetropic HIV-1 isolates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, Y -- Broder, C C -- Kennedy, P E -- Berger, E A -- New York, N.Y. -- Science. 1996 May 10;272(5263):872-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629022" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Antigens, CD4/*physiology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cell Membrane/virology ; Chemokines/physiology ; *Cloning, Molecular ; DNA, Complementary/genetics ; Disease Models, Animal ; GTP-Binding Proteins/metabolism ; Giant Cells ; HIV Envelope Protein gp120/physiology ; HIV-1/*pathogenicity/physiology ; HeLa Cells ; Humans ; Leukocytes, Mononuclear/virology ; Macrophages/virology ; *Membrane Fusion ; Membrane Proteins/genetics/*physiology ; Mice ; Molecular Sequence Data ; RNA, Messenger/metabolism ; Receptors, CXCR4 ; Recombinant Proteins ; Transfection
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  • 42
    Publication Date: 1996-11-01
    Description: Listeria monocytogenes is a bacterial pathogen that invades cultured nonphagocytic cells. Inhibitors and a dominant negative mutation were used to demonstrate that efficient entry requires the phosphoinositide (PI) 3-kinase p85alpha-p110. Infection with L. monocytogenes caused rapid increases in cellular amounts of PI(3, 4)P2 and PI(3,4,5)P3, indicating that invading bacteria stimulated PI 3-kinase activity. This stimulation required the bacterial protein InlB, host cell tyrosine phosphorylation, and association of p85alpha with one or more tyrosine-phosphorylated proteins. This role for PI 3-kinase in bacterial entry may have parallels in some endocytic events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ireton, K -- Payrastre, B -- Chap, H -- Ogawa, W -- Sakaue, H -- Kasuga, M -- Cossart, P -- New York, N.Y. -- Science. 1996 Nov 1;274(5288):780-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unite des Interactions Bacteries-Cellules, Institut Pasteur, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8864117" target="_blank"〉PubMed〈/a〉
    Keywords: Androstadienes/pharmacology ; Animals ; Bacterial Proteins/physiology ; Cell Line ; Chromones/pharmacology ; Cytochalasin D/pharmacology ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Genistein ; Humans ; Isoflavones/pharmacology ; Listeria monocytogenes/*enzymology/*pathogenicity ; Membrane Proteins/physiology ; Morpholines/pharmacology ; Phosphatidylinositol 3-Kinases ; Phosphatidylinositol Phosphates/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/*metabolism ; Phosphotyrosine/metabolism ; Tumor Cells, Cultured
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-15
    Description: Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, B -- Novick, D -- Rubinstein, M -- New York, N.Y. -- Science. 1996 Nov 15;274(5290):1185-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. lvrub@weizmann.weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8895466" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Carrier Proteins/genetics/metabolism ; Cell Line ; Down-Regulation/drug effects ; GRB2 Adaptor Protein ; Gene Expression Regulation, Enzymologic/drug effects ; Gluconeogenesis/drug effects ; Glucose/metabolism ; Humans ; Insulin/*pharmacology ; Insulin Antagonists ; Insulin Receptor Substrate Proteins ; Leptin ; Liver/cytology/metabolism ; Phosphatidylinositol 3-Kinases ; Phosphoenolpyruvate Carboxykinase (GTP)/genetics/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Phosphotyrosine/metabolism ; Proteins/metabolism/*pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, Insulin/metabolism ; *Receptors, Cell Surface ; Receptors, Leptin ; Signal Transduction ; Tumor Cells, Cultured
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  • 44
    Publication Date: 1996-05-24
    Description: The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plas, D R -- Johnson, R -- Pingel, J T -- Matthews, R J -- Dalton, M -- Roy, G -- Chan, A C -- Thomas, M L -- New York, N.Y. -- Science. 1996 May 24;272(5265):1173-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Center for Immunology, Washington University Medical School, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Mutation ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; T-Lymphocytes/immunology/*metabolism ; Transfection ; Tumor Cells, Cultured ; ZAP-70 Protein-Tyrosine Kinase ; src-Family Kinases/metabolism
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-04-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, J -- New York, N.Y. -- Science. 1996 Apr 12;272(5259):195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8602502" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/virology ; Cell Line ; Gene Products, vpr/physiology ; *Gene Transfer Techniques ; Genes, Viral ; *Genetic Therapy ; *Genetic Vectors ; HIV/*genetics/physiology ; Humans ; Neurons/virology ; Viral Matrix Proteins/physiology ; vpr Gene Products, Human Immunodeficiency Virus
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  • 46
    Publication Date: 1996-10-04
    Description: Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Altman, J D -- Moss, P A -- Goulder, P J -- Barouch, D H -- McHeyzer-Williams, M G -- Bell, J I -- McMichael, A J -- Davis, M M -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1996 Oct 4;274(5284):94-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5428, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8810254" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, Viral/*immunology ; Base Sequence ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Coloring Agents ; Epitopes/immunology ; Flow Cytometry ; Gene Products, gag/immunology ; HIV Seropositivity/*immunology ; HLA-A2 Antigen/*immunology ; Humans ; Molecular Sequence Data ; Peptide Fragments/*immunology ; Phenotype ; RNA-Directed DNA Polymerase/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Matrix Proteins/immunology
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, J -- New York, N.Y. -- Science. 1996 May 10;272(5263):809-10.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629006" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/*physiology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cell Membrane/*virology ; Chemokines/physiology ; DNA, Complementary ; HIV/*pathogenicity/physiology ; HIV Infections/drug therapy/immunology/virology ; Humans ; *Membrane Fusion ; Membrane Proteins/genetics/*physiology ; Receptors, CXCR4 ; Transfection
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  • 48
    Publication Date: 1996-03-15
    Description: Multivalent binding proteins, such as the yeast scaffold protein Sterile-5, coordinate the location of kinases by serving as platforms for the assembly of signaling units. Similarly, in mammalian cells the cyclic adenosine 3',5'-monophosphate-dependent protein kinase (PKA) and phosphatase 2B [calcineurin (CaN)] are complexed by an A kinase anchoring protein, AKAP79. Deletion analysis and binding studies demonstrate that a third enzyme, protein kinase C (PKC), binds AKAP79 at a site distinct from those bound by PKA or CaN. The subcellular distributions of PKC and AKAP79 were similar in neurons. Thus, AKAP79 appears to function as a scaffold protein for three multifunctional enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klauck, T M -- Faux, M C -- Labudda, K -- Langeberg, L K -- Jaken, S -- Scott, J D -- CA538841/CA/NCI NIH HHS/ -- GM48231/GM/NIGMS NIH HHS/ -- GM50152/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Mar 15;271(5255):1589-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, Portland, 97201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599116" target="_blank"〉PubMed〈/a〉
    Keywords: A Kinase Anchor Proteins ; *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Brain/enzymology ; Calcineurin ; Calmodulin/pharmacology ; Calmodulin-Binding Proteins/*metabolism ; *Carrier Proteins ; Cattle ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/analysis/antagonists & ; inhibitors/*metabolism ; Fungal Proteins/metabolism ; Humans ; Molecular Sequence Data ; Neurons/chemistry ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; Protein Kinase C/analysis/antagonists & inhibitors/*metabolism ; Proteins/analysis/*metabolism/pharmacology ; Recombinant Proteins ; *Saccharomyces cerevisiae Proteins ; Signal Transduction ; Synapses/physiology
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  • 49
    Publication Date: 1996-05-03
    Description: Signal transducers and activators of transcription (STAT) proteins can be conditionally activated in response to epidermal growth factor (EGF) and interferon (IFN)-gamma. STAT activation was correlated with cell growth inhibition in response to EGF and IFN-gamma. Activated STAT proteins specifically recognized the conserved STAT-responsive elements in the promoter of the gene encoding the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/CIP1 and regulated the induction of p21 messenger RNA. IFN-gamma did not inhibit the growth of U3A cells, which are deficient in STAT1, but did inhibit the growth of U3A cells into which STAT1 alpha was reintroduced. Thus, STAT1 protein is essential for cell growth suppression in response to IFN-gamma. The STAT signaling pathway appears to negatively regulate the cell cycle by inducing CDK inhibitors in response to cytokines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chin, Y E -- Kitagawa, M -- Su, W C -- You, Z H -- Iwamoto, Y -- Fu, X Y -- R01 AI34522/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 May 3;272(5262):719-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614832" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; *Cell Division/drug effects ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/biosynthesis/*genetics ; DNA/biosynthesis ; DNA-Binding Proteins/metabolism/*physiology ; Epidermal Growth Factor/pharmacology ; *Gene Expression Regulation ; Humans ; Interferon-gamma/pharmacology ; Molecular Sequence Data ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; *Signal Transduction ; Trans-Activators/metabolism/*physiology ; Transfection ; Tumor Cells, Cultured
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  • 50
    Publication Date: 1996-07-19
    Description: CD1 proteins have been implicated as antigen-presenting molecules for T cell-mediated immune responses, but their intracellular localization and trafficking remain uncharacterized. CD1b, a member of this family that presents microbial lipid antigens of exogenous origin, was found to localize to endocytic compartments that included the same specialized subset of endosomes in which major histocompatibility complex (MHC) class II molecules are proposed to bind endocytosed antigens. Unlike MHC class II molecules, which traffic to antigen-loading endosomal compartments [MHC class II compartments (MIICs)] primarily as a consequence of their association with the invariant chain, localization of CD1b to these compartments was dependent on a tyrosine-based motif in its own cytoplasmic tail.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugita, M -- Jackman, R M -- van Donselaar, E -- Behar, S M -- Rogers, R A -- Peters, P J -- Brenner, M B -- Porcelli, S A -- New York, N.Y. -- Science. 1996 Jul 19;273(5273):349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662520" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD1/analysis/chemistry/*metabolism ; B-Lymphocytes ; Base Sequence ; Cell Compartmentation ; Cell Line ; Cell Membrane/immunology ; Coated Pits, Cell-Membrane/immunology ; Endocytosis ; Endosomes/*immunology/ultrastructure ; HLA-D Antigens/analysis ; HeLa Cells ; Histocompatibility Antigens Class II/analysis/*metabolism ; Humans ; Microscopy, Immunoelectron ; Molecular Sequence Data ; Monocytes/immunology ; Transfection
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  • 51
    Publication Date: 1996-12-06
    Description: Four virus proteins similar to two human macrophage inflammatory protein (MIP) chemokines, interleukin-6 (IL-6), and interferon regulatory factor (IRF) are encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 was functional in B9 proliferation assays and primarily expressed in KSHV-infected hematopoietic cells rather than KS lesions. HIV-1 transmission studies showed that vMIP-I is similar to human MIP chemokines in its ability to inhibit replication of HIV-1 strains dependent on the CCR5 co-receptor. These viral genes may form part of the response to host defenses contributing to virus-induced neoplasia and may have relevance to KSHV and HIV-I interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, P S -- Boshoff, C -- Weiss, R A -- Chang, Y -- CA67391/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 6;274(5293):1739-44.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Public Health, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8939871" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Division ; Cell Line ; Chemokine CCL4 ; Gene Expression ; Genes, Viral ; HIV-1/physiology ; Herpesvirus 4, Human/physiology ; Herpesvirus 8, Human/*genetics/physiology ; Humans ; Interleukin-6/chemistry/genetics ; Lymph Nodes/virology ; Lymphoma, B-Cell/virology ; Macrophage Inflammatory Proteins/chemistry/genetics ; Mice ; *Molecular Mimicry ; Molecular Sequence Data ; Receptors, CCR5 ; Receptors, Cytokine/metabolism ; Receptors, HIV/metabolism ; Sarcoma, Kaposi/virology ; Sequence Alignment ; Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Tumor Cells, Cultured ; Viral Nonstructural Proteins/chemistry/*genetics/physiology ; Virus Replication
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-17
    Description: The vectorial movement of proteins requires specific recognition by components of the vesicular trafficking machinery. A protein, sorting nexin-1 (SNX1), was identified in a human cell line that bound to a region of the epidermal growth factor receptor (EGFR) containing the lysosomal targeting code. SNX1 contains a region of homology to a yeast vacuolar sorting protein, and overexpression of SNX1 decreased the amount of EGFR on the cell surface as a result of enhanced rates of constitutive and ligand-induced degradation. Thus, SNX1 is likely to play a role in sorting EGFR to lysosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurten, R C -- Cadena, D L -- Gill, G N -- CA58689/CA/NCI NIH HHS/ -- F32DK08666/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1996 May 17;272(5264):1008-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Diego, La Jolla 92093-0650, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638121" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cell Membrane/*metabolism ; Down-Regulation ; Endocytosis ; Epidermal Growth Factor/pharmacology ; HeLa Cells ; Humans ; Ligands ; Lysosomes/*metabolism ; Molecular Sequence Data ; Molecular Weight ; Receptor, Epidermal Growth Factor/*metabolism ; Transfection ; *Vesicular Transport Proteins
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  • 53
    Publication Date: 1996-05-03
    Description: The P2Z receptor is responsible for adenosine triphosphate (ATP)-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Other ATP-gated channels, the P2X receptors, are permeable only to small cations. Here, an ATP receptor, the P2X7 receptor, was cloned from rat brain and exhibited both these properties. This protein is homologous to other P2X receptors but has a unique carboxyl-terminal domain that was required for the lytic actions of ATP. Thus, the P2X7 (or P2Z) receptor is a bifunctional molecule that could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Surprenant, A -- Rassendren, F -- Kawashima, E -- North, R A -- Buell, G -- New York, N.Y. -- Science. 1996 May 3;272(5262):735-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Glaxo Institute for Molecular Biology, Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614837" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/analogs & derivatives/*metabolism/pharmacology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cations, Divalent/pharmacology ; Cell Death ; Cell Line ; Cloning, Molecular ; DNA, Complementary/genetics ; Electric Conductivity ; Humans ; Ion Channels/physiology ; Mice ; Molecular Sequence Data ; Patch-Clamp Techniques ; Rats ; Receptors, Purinergic P2/chemistry/genetics/*physiology ; Receptors, Purinergic P2X7 ; Transfection
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  • 54
    Publication Date: 1996-09-20
    Description: Anandamide is an endogenous ligand for central cannabinoid receptors and is released after neuronal depolarization. Anandamide increased protein tyrosine phosphorylation in rat hippocampal slices and neurons in culture. The action of anandamide resulted from the inhibition of adenylyl cyclase and cyclic adenosine 3', 5'-monophosphate-dependent protein kinase. One of the proteins phosphorylated in response to anandamide was an isoform of pp125-focal adhesion kinase (FAK+) expressed preferentially in neurons. Focal adhesion kinase is a tyrosine kinase involved in the interactions between the integrins and actin-based cytoskeleton. Thus, anandamide may exert neurotrophic effects and play a role in synaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Derkinderen, P -- Toutant, M -- Burgaya, F -- Le Bert, M -- Siciliano, J C -- de Franciscis, V -- Gelman, M -- Girault, J A -- New York, N.Y. -- Science. 1996 Sep 20;273(5282):1719-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U 114, Chaire de Neuropharmacologie, College de France, 11 place Marcelin Berthelot, 75231 Paris cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8781236" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Animals ; Arachidonic Acid/pharmacology ; Arachidonic Acids/*pharmacology ; Cell Adhesion Molecules/*metabolism ; Cell Line ; Cells, Cultured ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Endocannabinoids ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Hippocampus/drug effects/*enzymology ; In Vitro Techniques ; Molecular Sequence Data ; Neuronal Plasticity/drug effects ; Neurons/drug effects/*enzymology ; Phosphorylation ; Phosphotyrosine/metabolism ; Polyunsaturated Alkamides ; Prosencephalon ; Protein-Tyrosine Kinases/*metabolism ; Rats ; Receptors, Cannabinoid ; Receptors, Drug/metabolism
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  • 55
    Publication Date: 1996-08-16
    Description: The Tax transactivator of the human T cell leukemia virus type I (HTLV-I) exhibits oncogenic properties. A screen for proteins interacting with Tax yielded a complementary DNA (cDNA) encoding the human Int-6 protein. In mice, the Int-6 gene can be converted into a putative dominant negative oncogene after retroviral insertion. Here, Int-6 was localized in the cell nucleus to give a speckled staining pattern superposed to that of the promyelocytic leukemia (PML) protein. The binding of Tax to Int-6 caused its redistribution from the nuclear domains to the cytoplasm. Thus, Int-6 is a component of the PML nuclear bodies and Tax disrupts its normal cellular localization by binding to it.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desbois, C -- Rousset, R -- Bantignies, F -- Jalinot, P -- New York, N.Y. -- Science. 1996 Aug 16;273(5277):951-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre National de la Recherche Scientifique UMR49, Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8688078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Nucleus/*chemistry ; Cytoplasm/chemistry ; Eukaryotic Initiation Factor-3 ; Gene Products, tax/analysis/*metabolism ; HeLa Cells ; Humans ; Mice ; *Neoplasm Proteins ; *Nuclear Proteins ; Proto-Oncogene Proteins/analysis/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/*analysis ; Transfection ; Tumor Suppressor Proteins
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  • 56
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-01-26
    Description: Most nonmalignant cells are anchorage-dependent; they require substrate attachment for growth and, in some instances, survival. This requirement is lost on oncogenic transformation. The cyclin E-CDK2 complex, which is required for the G1-S transition of the cell cycle, was activated in late G1 phase in attached human fibroblasts, but not in fibroblasts maintained in suspension. In transformed fibroblasts the complex was active regardless of attachment. The lack of cyclin E-CDK2 activity in suspended cells appeared to result from increased expression of CDK2 inhibitors and a concomitant decrease in phosphorylation of CDK2 on threonine-160. Suppression of cyclin E-CDK2 activity may thus underlie the anchorage dependence of cell growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fang, F -- Orend, G -- Watanabe, N -- Hunter, T -- Ruoslahti, E -- CA 28896/CA/NCI NIH HHS/ -- CA 60725/CA/NCI NIH HHS/ -- CA 67224/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Jan 26;271(5248):499-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉La Jolla Cancer Research Foundation, Cancer Center, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8560263" target="_blank"〉PubMed〈/a〉
    Keywords: *CDC2-CDC28 Kinases ; *Cell Adhesion ; *Cell Cycle Proteins ; Cell Line ; Cell Line, Transformed ; Cell Nucleus/metabolism ; *Cell Transformation, Neoplastic ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclin-Dependent Kinase Inhibitor p57 ; Cyclin-Dependent Kinases/antagonists & inhibitors/*metabolism ; Cyclins/*metabolism ; Enzyme Inhibitors/metabolism ; *G1 Phase ; Humans ; Microtubule-Associated Proteins/metabolism ; Nuclear Proteins/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism ; Tumor Cells, Cultured ; *Tumor Suppressor Proteins
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  • 57
    Publication Date: 1996-05-24
    Description: Transforming growth factor-beta (TGF-beta) regulates many aspects of cellular function. A member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, TAK1, was previously identified as a mediator in the signaling pathway of TGF-beta superfamily members. The yeast two-hybrid system has now revealed two human proteins, termed TAB1 and TAB2 (for TAK1 binding protein), that interact with TAK1. TAB1 and TAK1 were co-immunoprecipitated from mammalian cells. Overproduction of TAB1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by TGF-beta, and increased the kinase activity of TAK1. TAB1 may function as an activator of the TAK1 MAPKKK in TGF-beta signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shibuya, H -- Yamaguchi, K -- Shirakabe, K -- Tonegawa, A -- Gotoh, Y -- Ueno, N -- Irie, K -- Nishida, E -- Matsumoto, K -- New York, N.Y. -- Science. 1996 May 24;272(5265):1179-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638164" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/chemistry/*metabolism ; Cell Line ; Cloning, Molecular ; Enzyme Activation ; Genes, Reporter ; Humans ; *Intracellular Signaling Peptides and Proteins ; *MAP Kinase Kinase Kinases ; Mice ; Molecular Sequence Data ; Plasminogen Activator Inhibitor 1/genetics ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/*metabolism ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; *Signal Transduction ; Transfection ; Transformation, Genetic ; Transforming Growth Factor beta/*metabolism
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  • 58
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-01-26
    Description: The CD44 family of surface receptors regulates adhesion, movement, and activation of normal and neoplastic cells. The cytokine osteopontin (Eta-1), which regulates similar cellular functions, was found to be a protein ligand of CD44. Osteopontin induces cellular chemotaxis but not homotypic aggregation, whereas the inverse is true for the interaction between CD44 and a carbohydrate ligand, hyaluronate. The different responses of cells after CD44 ligation by either osteopontin or hyaluronate may account for the independent effects of CD44 on cell migration and growth. This mechanism may also be exploited by tumor cells to promote metastasis formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weber, G F -- Ashkar, S -- Glimcher, M J -- Cantor, H -- AI12184/AI/NIAID NIH HHS/ -- AI13600/AI/NIAID NIH HHS/ -- P01 AR34078/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jan 26;271(5248):509-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8560266" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD44/*metabolism ; Base Sequence ; *Cell Adhesion ; Cell Aggregation ; Cell Line ; *Chemotaxis ; Cytokines/*metabolism/pharmacology ; Hyaluronic Acid/metabolism/pharmacology ; Ligands ; Mice ; Molecular Sequence Data ; Monocytes/metabolism ; Oligopeptides/pharmacology ; Osteopontin ; Sialoglycoproteins/*metabolism/pharmacology ; Transfection ; Tumor Cells, Cultured
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  • 59
    Publication Date: 1996-12-20
    Description: An important feature of the human immune system is the ability of T cells to respond to small quantities of antigen. Class II major histocompatibility complex (MHC)-restricted T cells that expressed a costimulatory natural killer (NK) cell receptor for class I MHC proteins were cloned. In the presence of low doses of superantigen, the proliferative response of these T cell clones was three- to ninefold greater when the T cells were costimulated by way of the NK receptor. Thus, the action of costimulatory NK receptors on T cells may play a significant role in initiating and sustaining immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mandelboim, O -- Davis, D M -- Reyburn, H T -- Vales-Gomez, M -- Sheu, E G -- Pazmany, L -- Strominger, J L -- CA 47554/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2097-100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA. jlstrom@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953044" target="_blank"〉PubMed〈/a〉
    Keywords: B-Lymphocytes/immunology ; Cell Line ; Clone Cells ; HLA Antigens/immunology ; HLA-C Antigens/immunology ; HLA-G Antigens ; Histocompatibility Antigens Class I/*immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; *Lymphocyte Activation ; Receptors, Immunologic/*immunology ; Superantigens/immunology ; T-Lymphocytes/*immunology ; Transfection
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  • 60
    Publication Date: 1996-11-29
    Description: The 3' ends of most eukaryotic messenger RNAs are generated by endonucleolytic cleavage and polyadenylation. In mammals, the cleavage and polyadenylation specificity factor (CPSF) plays a central role in both steps of the processing reaction. Here, the cloning of the 73-kilodalton subunit of CPSF is reported. Sequence analyses revealed that a yeast protein (Ysh1) was highly similar to the 73-kD polypeptide. Ysh1 constitutes a new subunit of polyadenylation factor I (PFI), which has a role in yeast pre-mRNA 3'-end formation. This finding was unexpected because in contrast to CPSF, PFI is only required for the polyadenylation reaction. These results contribute to the understanding of how 3'-end processing factors may have evolved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jenny, A -- Minvielle-Sebastia, L -- Preker, P J -- Keller, W -- New York, N.Y. -- Science. 1996 Nov 29;274(5292):1514-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland. Keller2@ubaclu.unibas.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8929409" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cloning, Molecular ; Evolution, Molecular ; Fungal Proteins/*chemistry/genetics/metabolism ; Humans ; Molecular Sequence Data ; Molecular Weight ; Poly A/metabolism ; Polynucleotide Adenylyltransferase/metabolism ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Fungal/metabolism ; RNA, Messenger/metabolism ; RNA-Binding Proteins/*chemistry/genetics/metabolism ; Sequence Homology, Amino Acid ; mRNA Cleavage and Polyadenylation Factors
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  • 61
    Publication Date: 1996-05-24
    Description: Little is known about the integral membrane proteins that participate in the early secretory pathway of mammalian cells. The complementary DNA encoding a 28-kilodalton protein (p28) of the cis-Golgi was cloned and sequenced. The protein was predicted to contain a central coiled-coil domain with a carboxyl-terminal membrane anchor. An in vitro assay for endoplasmic reticulum-Golgi transport was used to show that p28 participates in the docking and fusion stage of this transport event. Biochemical studies established that p28 is a core component of the Golgi SNAP receptor (SNARE) complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subramaniam, V N -- Peter, F -- Philp, R -- Wong, S H -- Hong, W -- New York, N.Y. -- Science. 1996 May 24;272(5265):1161-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Membrane Biology Laboratory, Institute of Molecular and Cell Biology, National University of Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638159" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Biological Transport ; Carrier Proteins/analysis ; Cell Line ; Cloning, Molecular ; DNA, Complementary/genetics ; Egtazic Acid/pharmacology ; Endoplasmic Reticulum/*metabolism ; Golgi Apparatus/*chemistry/metabolism ; *Membrane Glycoproteins ; Membrane Proteins/analysis/*chemistry/genetics/isolation & ; purification/*metabolism ; Molecular Sequence Data ; N-Ethylmaleimide-Sensitive Proteins ; SNARE Proteins ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins ; *Vesicular Transport Proteins ; Vesicular stomatitis Indiana virus ; Viral Envelope Proteins/metabolism
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  • 62
    Publication Date: 1996-05-17
    Description: The adenomatous polyposis coli gene (APC) is mutated in most colon cancers. The APC protein binds to the cellular adhesion molecule beta-catenin, which is a mammalian homolog of ARMADILLO, a component of the WINGLESS signaling pathway in Drosophila development. Here it is shown that when beta-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3beta (GSK3beta), a mammalian homolog of Drosophila ZESTE WHITE 3. APC was a good substrate for GSK3 beta in vitro, and the phosphorylation sites were mapped to the central region of APC. Binding of beta-catenin to this region was dependent on phosphorylation by GSK3 beta.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rubinfeld, B -- Albert, I -- Porfiri, E -- Fiol, C -- Munemitsu, S -- Polakis, P -- New York, N.Y. -- Science. 1996 May 17;272(5264):1023-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Onyx Pharmaceuticals, Richmond, CA 94806, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638126" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein ; Animals ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cell Line ; Cytoskeletal Proteins/*metabolism ; Glycogen Synthase Kinase 3 ; Glycogen Synthase Kinases ; Humans ; Mice ; Mutation ; Phosphorylation ; Protein Binding ; *Trans-Activators ; Tumor Cells, Cultured ; beta Catenin
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  • 63
    Publication Date: 1996-10-25
    Description: Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors. Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120. The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots. No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells. However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lapham, C K -- Ouyang, J -- Chandrasekhar, B -- Nguyen, N Y -- Dimitrov, D S -- Golding, H -- New York, N.Y. -- Science. 1996 Oct 25;274(5287):602-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8849450" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Antigens, CD4/immunology/*metabolism ; Cell Line ; Cell Membrane/*metabolism ; Giant Cells ; HIV Envelope Protein gp120/immunology/*metabolism/pharmacology ; Humans ; Immunoblotting ; Membrane Fusion ; Membrane Proteins/chemistry/immunology/*metabolism ; Mice ; Molecular Sequence Data ; Molecular Weight ; Precipitin Tests ; Receptors, CXCR4 ; Receptors, HIV/chemistry/immunology/*metabolism ; T-Lymphocytes ; Tetradecanoylphorbol Acetate/pharmacology ; Vaccinia virus/genetics/physiology
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  • 64
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-02-02
    Description: Quaternary ammonium blockers inhibit many voltage-activated potassium (K+) channels from the intracellular side. When applied to Drosophila Shaker potassium channels expressed in mammalian cells, these rapidly reversible blockers produced use-dependent inhibition through an unusual mechanism--they promoted an intrinsic conformational change known as C-type inactivation, from which recovery is slow. The blockers did so by cutting off potassium ion flow to a site in the pore, which then emptied at a rate of 10(5) ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10(7) per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baukrowitz, T -- Yellen, G -- NS29693/NS/NINDS NIH HHS/ -- R01 NS029693/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):653-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571129" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Line ; Humans ; Lidocaine/analogs & derivatives/metabolism/pharmacology ; Potassium/*metabolism ; *Potassium Channel Blockers ; Potassium Channels/metabolism ; Quaternary Ammonium Compounds/metabolism/*pharmacology ; Shaker Superfamily of Potassium Channels ; Tetraethylammonium Compounds/metabolism/pharmacology
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  • 65
    Publication Date: 1996-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scully, R -- Ganesan, S -- Brown, M -- De Caprio, J A -- Cannistra, S A -- Feunteun, J -- Schnitt, S -- Livingston, D M -- New York, N.Y. -- Science. 1996 Apr 5;272(5258):123-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8600523" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; BRCA1 Protein ; Breast Neoplasms/*chemistry/ultrastructure ; Cell Line ; Cell Nucleus/*chemistry ; Cytoplasm/chemistry ; Female ; Fluorescent Antibody Technique ; Histocytological Preparation Techniques ; Humans ; Immunoenzyme Techniques ; Molecular Sequence Data ; Neoplasm Proteins/*analysis/immunology ; Ovarian Neoplasms/*chemistry/ultrastructure ; Transcription Factors/*analysis/immunology ; Tumor Cells, Cultured
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  • 66
    Publication Date: 1996-01-19
    Description: beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of beta-arrestins in human embryonic kidney cells rescued the sequestration of beta 2-adrenergic receptor (beta 2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of beta-adrenergic receptor kinase 1. Wild-type beta 2AR sequestration was inhibited by the overexpression of two beta-arrestin mutants. These findings suggest that beta-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferguson, S S -- Downey, W E 3rd -- Colapietro, A M -- Barak, L S -- Menard, L -- Caron, M G -- NS 19576/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jan 19;271(5247):363-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Laboratory, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8553074" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Agonists/*pharmacology ; Antigens/genetics/*physiology ; *Arrestins ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism ; DNA, Complementary ; Eye Proteins/genetics/*physiology ; GTP-Binding Proteins/*metabolism ; Humans ; Isoproterenol/pharmacology ; Mutation ; Phosphorylation ; Point Mutation ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Transfection ; beta-Adrenergic Receptor Kinases
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-10-04
    Description: Hepatitis delta virus (HDV) is a pathogenic human virus whose RNA genome and replication cycle resemble those of plant viroids. However, viroid genomes contain no open reading frames, whereas HDV RNA encodes a single protein, hepatitis delta antigen (HDAg), which is required for viral replication. A cellular gene whose product interacts with HDAg has now been identified, and this interaction was found to affect viral genomic replication in intact cells. DNA sequence analysis revealed that this protein, termed delta-interacting protein A (DIPA), is a cellular homolog of HDAg. These observations demonstrate that a host gene product can modulate HDV replication and suggest that HDV may have evolved from a primitive viroidlike RNA through capture of a cellular transcript.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brazas, R -- Ganem, D -- New York, N.Y. -- Science. 1996 Oct 4;274(5284):90-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8810253" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; *Biological Evolution ; Carrier Proteins/*chemistry/genetics/metabolism ; Cell Line ; Cloning, Molecular ; Genome, Viral ; Hepatitis Antigens/*chemistry/genetics/*metabolism ; Hepatitis Delta Virus/*genetics/physiology ; Hepatitis delta Antigens ; Humans ; Liver/chemistry ; Molecular Sequence Data ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Repressor Proteins ; Sequence Alignment ; Transfection ; Tumor Cells, Cultured ; Viroids/genetics ; Virus Replication
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  • 68
    Publication Date: 1996-11-01
    Description: The outermost layer of the human placenta is devoid of classical class I human leukocyte antigens (HLA-A, HLA-B, and HLA-C) and class II proteins (HLA-DR, HLA-DQ, and HLA-DP). Although this prevents recognition by maternal T lymphocytes, the lack of class I molecules leaves these cells susceptible to attack by natural killer (NK) cells. However, trophoblast cells directly in contact with the maternal tissues express the class I molecule HLA-G, which may be involved in protecting the trophoblast from recognition by NK cells. Here evidence is provided that expression of HLA-G is sufficient to protect otherwise susceptible target cells from lysis by activated NK1 and NK2 cell lines and clones that are specific for distinct groups of HLA-C alleles. The receptors on NK cells that recognize HLA-G are also identified.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pazmany, L -- Mandelboim, O -- Vales-Gomez, M -- Davis, D M -- Reyburn, H T -- Strominger, J L -- CA-47554/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Nov 1;274(5288):792-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8864122" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD56/analysis ; Cell Line ; Clone Cells ; *Cytotoxicity, Immunologic ; HLA Antigens/genetics/*physiology ; HLA-C Antigens/genetics/physiology ; HLA-G Antigens ; Histocompatibility Antigens Class I/genetics/*physiology ; Humans ; Killer Cells, Natural/*immunology ; Receptors, Immunologic/physiology ; Receptors, KIR ; Transfection ; Tumor Cells, Cultured
    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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  • 69
    Publication Date: 1996-09-13
    Description: Integrin function is central to inflammation, immunity, and tumor progression. The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR. Interaction of soluble uPAR with the active conformer of integrins mimicked the inhibitory effects of membrane uPAR. Both uPAR-mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes. These data provide a paradigm for regulation of integrins in which a nonintegrin membrane receptor interacts with and modifies the function of activated integrins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, Y -- Lukashev, M -- Simon, D I -- Bodary, S C -- Rosenberg, S -- Doyle, M V -- Chapman, H A -- HD 26732/HD/NICHD NIH HHS/ -- HL 02768/HL/NHLBI NIH HHS/ -- HL44712/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Sep 13;273(5281):1551-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8703217" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD18/metabolism ; Antigens, CD29/metabolism ; *Cell Adhesion ; Cell Line ; Fibronectins/metabolism ; Glycosylphosphatidylinositols/metabolism ; Humans ; Integrins/metabolism/*physiology ; Ligands ; Molecular Sequence Data ; Receptors, Cell Surface/*metabolism ; Receptors, Cytoadhesin/*metabolism ; Receptors, Urokinase Plasminogen Activator ; Recombinant Fusion Proteins/metabolism ; Transfection ; Urokinase-Type Plasminogen Activator/metabolism ; Vitronectin/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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  • 70
    Publication Date: 1996-07-26
    Description: Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wrighton, N C -- Farrell, F X -- Chang, R -- Kashyap, A K -- Barbone, F P -- Mulcahy, L S -- Johnson, D L -- Barrett, R W -- Jolliffe, L K -- Dower, W J -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):458-64.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662529" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacteriophages ; Cell Division/drug effects ; Cell Line ; Cloning, Molecular ; Erythropoiesis/drug effects ; Erythropoietin/chemistry/*metabolism/*pharmacology ; Humans ; Ligands ; Mice ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis ; Peptides, Cyclic/chemistry/*metabolism/*pharmacology ; Phosphorylation ; Protein Structure, Secondary ; Receptors, Erythropoietin/*agonists/chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Transduction ; Solubility ; Tyrosine/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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