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  • 1
    Electronic Resource
    Electronic Resource
    Cascade of autophosphorylation in the β-subunit of the insulin receptor (1989)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 39 (1989), S. 429-441 
    Details
    ISSN: 0730-2312
    Keywords: transmembrane signal ; protein phosphorylation ; tyrosine kinase ; signal transmission ; phosphorylation cascade ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Insulin stimulated autophosphorylation of the β-subunit of the insulin receptor purified from Fao hepatoma cells or purified from Chinese hamster ovary (CHO/HIRC) or Swiss 3T3 (3T3/HIRC) cells transfected with the wild-type human insulin receptor cDNA. Autophosphorylation of the purified receptor occurred in at least two regions of the β-subunit: the regulatory region containing Tyr-1146, Tyr-1150, and Tyr-1151, and the C-terminus containing Tyr-1316 and Tyr-1322. In the presence of antiphosphotyrosine antibody (α-PY), autophosphorylation of the purified receptor was inhibited nearly 80% during insulin stimulation. Tryptic peptide mapping showed that α-PY inhibited autophosphorylation of both tyrosyl residues in the C-terminus and one tyrosyl residue in the regulatory region, either Tyr-1150 or Tyr-1151. Thus, a bis-phosphorylated form of the regulatory region accumulated in the presence of α-PY, which contained Tyr(P)-1146 and either Tyr(P)-1150 or 1151. In intact Fao, CHO/HIRC, and 3T3/HIRC cells, insulin stimulated tyrosyl phosphorylation of the β-subunit of the insulin receptor. Tryptic peptide mapping indicated that the regulatory region of the β-subunit was mainly (〉80%) bis-phosphorylated; however, all three tyrosyl residues of the regulatory region were phosphorylated in about 20% of the receptors. As the phosphotransferase was activated by tris-phosphorylation but not bis-phosphorylation of the regulatory region of the β-subunit (White et al.: Journal of Biological Chemistry 263:2969-2980, 1988), the extent of autophosphorylation in the regulatory region may play an important regulatory role during signal transmission in the intact cell.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240390409
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Phosphorylation of glycolytic and gluconeogenic enzymes by the insulin receptor kinase (1987)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 33 (1987), S. 15-26 
    Details
    ISSN: 0730-2312
    Keywords: phosphorylation ; insulin receptor ; tyrosine kinase ; phosphofructokinase ; glycolysis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Various glycolytic and gluconeogenic enzymes were tested as substrates for the insulin receptor kinase. Phosphofructokinase and phosphoglycerate mutase were found to be the best substrates. Phosphorylation of these enzymes was rapid, stimulated 2- to 6-fold by 10-7 M insulin and occurred exclusively on tyrosine residues. Enolase, fructose 1,6-bisphosphatase, lactate dehydrogenases in decreasing order, were also subject to insulin-stimulated phosphorylation but to a smaller extent than that for phpsphofructokinase or phosphoglycerate mutase.The phosphorylation of phosphofructokinase was studied most extensively since phosphofructokinase is known to catalyze a rate-limiting step in glycolosis. The apparent Km of the insulin receptor for phosphofructokinase was 0.1 μM, which is within the physiologic range of concentration of this enzyme in most cells. Tyrosine phosphorylation of phosphofructokinase paralleled autophosphorylation of the β-subunit of the insulin receptor with respect to time course, insulin dose response (half maximal effect between 10-9 and 10-8 M insulin), and cation requirement (Mn2+ 〉 Mg2+ 〉 〉 Ca2+). Further study will be required to determine whether the tyrosine phosphorylation of phosphofructokinase plays a role in insulin-stimulated increases in glycolytic flux.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240330103
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  • 3
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    Smallpox transmission risks: how bad? (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, Laura H -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):50-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12102091" target="_blank"〉PubMed〈/a〉
    Keywords: *Air Microbiology ; Bioterrorism ; Disease Outbreaks ; Humans ; New York City/epidemiology ; Policy Making ; Smallpox/epidemiology/*transmission ; USSR/epidemiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Tumstatin, an endothelial cell-specific inhibitor of protein synthesis (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-01-05
    Description: Tumstatin is a 28-kilodalton fragment of type IV collagen that displays both anti-angiogenic and proapoptotic activity. Here we show that tumstatin functions as an endothelial cell-specific inhibitor of protein synthesis. Through a requisite interaction with alphaVbeta3 integrin, tumstatin inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3-kinase), protein kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR), and it prevents the dissociation of eukaryotic initiation factor 4E protein (eIF4E) from 4E-binding protein 1. These results establish a role for integrins in mediating cell-specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeshima, Yohei -- Sudhakar, Akulapalli -- Lively, Julie C -- Ueki, Kohjiro -- Kharbanda, Surender -- Kahn, C Ronald -- Sonenberg, Nahum -- Hynes, Richard O -- Kalluri, Raghu -- DK-51711/DK/NIDDK NIH HHS/ -- DK-55001/DK/NIDDK NIH HHS/ -- P01-HL66105/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 4;295(5552):140-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11778052" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Autoantigens/chemistry/metabolism/*pharmacology ; Carrier Proteins/metabolism ; Cattle ; Cells, Cultured ; Collagen Type IV/chemistry/metabolism/*pharmacology ; Endothelium, Vascular/*cytology/drug effects/*metabolism ; Enzyme Activation/drug effects ; Eukaryotic Initiation Factor-4E ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Mice ; Molecular Sequence Data ; Peptide Fragments/pharmacology ; Peptide Initiation Factors/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; *Protein Biosynthesis/drug effects ; Protein Kinase Inhibitors ; Protein Kinases/metabolism ; Protein Synthesis Inhibitors/*pharmacology ; *Protein-Serine-Threonine Kinases ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; RNA Caps/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Vitronectin/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; 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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  • 5
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    Molecular defects in insulin action (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, C R -- Goldstein, B J -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2662406" target="_blank"〉PubMed〈/a〉
    Keywords: Diabetes Mellitus/*physiopathology ; Humans ; Insulin/*physiology ; Insulin Resistance
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-01-26
    Description: The intracellular pathogen Legionella pneumophila subverts vesicle traffic in eukaryotic host cells to create a vacuole that supports replication. The dot/icm genes encode a protein secretion apparatus that L. pneumophila require for biogenesis of this vacuole. Here we show that L. pneumophila produce a protein called RalF that functions as an exchange factor for the ADP ribosylation factor (ARF) family of guanosine triphosphatases (GTPases). The RalF protein is required for the localization of ARF on phagosomes containing L. pneumophila. Translocation of RalF protein through the phagosomal membrane is a dot/icm-dependent process. Thus, RalF is a substrate of the Dot/Icm secretion apparatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagai, Hiroki -- Kagan, Jonathan C -- Zhu, Xinjun -- Kahn, Richard A -- Roy, Craig R -- R01 AI44371/AI/NIAID NIH HHS/ -- R29 AI41699/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 25;295(5555):679-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11809974" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factor 1/genetics/*metabolism ; ADP-Ribosylation Factors/metabolism ; Acanthamoeba/microbiology ; Amino Acid Sequence ; Animals ; Bacterial Proteins/genetics/metabolism ; Carrier Proteins/genetics/metabolism ; Cell Line ; Genes, Bacterial ; Guanine Nucleotide Exchange Factors/chemistry/genetics/*metabolism ; Humans ; Legionella/genetics ; Legionella pneumophila/genetics/growth & development/*metabolism ; Macrophages/microbiology ; Mice ; Mice, Inbred A ; Molecular Sequence Data ; Phagosomes/*metabolism/*microbiology ; Protein Structure, Tertiary ; Protein Transport ; RNA, Bacterial/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Homology, Amino Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Planning the genome institute's future (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uhlmann, Wendy R -- Bennett, Robin -- Botkin, Jeffrey R -- Botstein, David -- Boughman, Joann A -- Chakravarti, Aravinda -- Clayton, Ellen Wright -- Kahn, Jeffrey -- Koenig, Barbara -- Murray, Thomas H -- Olson, Maynard V -- Rowley, Janet -- Terry, Sharon -- Valle, David -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1515; author reply 1515.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624247" target="_blank"〉PubMed〈/a〉
    Keywords: *Genetic Research ; *Genome, Human ; *Genomics ; Human Genome Project ; Humans ; *National Institutes of Health (U.S.) ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Life scientists and the dual use dilemma (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, Laura H -- New York, N.Y. -- Science. 2003 Dec 12;302(5652):1894-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14671276" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethical Issues ; *Biological Science Disciplines ; Biomedical Research ; *Biotechnology ; Curriculum ; Humans ; *Research ; Research Personnel/*education ; Research Subjects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Molecular biology. HNFs--linking the liver and pancreatic islets in diabetes (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kulkarni, Rohit N -- Kahn, C Ronald -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1311-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. rohit.kulkarni@joslin.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988544" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; DNA-Binding Proteins/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; *Gene Expression Regulation ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 3-beta ; Hepatocyte Nuclear Factor 4 ; Hepatocyte Nuclear Factor 6 ; Hepatocytes/*metabolism ; Homeodomain Proteins/genetics/metabolism ; Humans ; Insulin/metabolism ; Insulin Resistance ; Islets of Langerhans/*metabolism ; Mice ; Mutation ; Nuclear Proteins/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/genetics/metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Signal Transduction ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
    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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  • 10
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    Human aging: usual and successful (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-07-10
    Description: Research in aging has emphasized average age-related losses and neglected the substantial heterogeneity of older persons. The effects of the aging process itself have been exaggerated, and the modifying effects of diet, exercise, personal habits, and psychosocial factors underestimated. Within the category of normal aging, a distinction can be made between usual aging, in which extrinsic factors heighten the effects of aging alone, and successful aging, in which extrinsic factors play a neutral or positive role. Research on the risks associated with usual aging and strategies to modify them should help elucidate how a transition from usual to successful aging can be facilitated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, J W -- Kahn, R L -- New York, N.Y. -- Science. 1987 Jul 10;237(4811):143-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3299702" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; *Aging/metabolism/physiology/psychology ; Carbohydrate Metabolism ; Cognition ; Cross-Sectional Studies ; Grief ; Health Promotion ; Health Services for the Aged ; Humans ; Longitudinal Studies ; Osteoporosis/physiopathology ; Patient Acceptance of Health Care ; Reference Values ; Social Support ; Volition
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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