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J. Biol. Chem., Vol. 269, Issue 45, 27920-27924, 11, 1994
MJ Quon, AJ Butte, MJ Zarnowski, G Sesti, SW Cushman and SI Taylor
Insulin signaling is initiated at least in part by activation of the
insulin receptor tyrosine kinase and subsequent phosphorylation of cellular
substrates such as insulin receptor substrate 1 (IRS-1). Previous studies
have focused on the role of IRS-1 in the mitogenic actions of insulin. We
have now investigated the possible role of IRS-1 in mediating the effect of
insulin to stimulate glucose transport in a physiologically relevant
insulin target tissue. In this study, we transfected rat adipose cells in
primary culture with an antisense ribozyme directed against rat IRS-1.
Expression of the ribozyme in these cells caused a 4.4-fold increase in the
concentration of insulin required to achieve half-maximal stimulation of
the translocation of cotransfected epitope-tagged GLUT4 without changing
the maximal insulin response. Overexpression of human IRS-1 increased the
basal cell surface GLUT4 to nearly the maximal level in the absence of
insulin. When the ribozyme (specific to rat IRS-1) was cotransfected along
with human IRS-1, the insulin dose-response curve was shifted to the left
when compared with cells transfected with the ribozyme alone. These data
provide strong support for the hypothesis that IRS-1 plays a role in
insulin-stimulated glucose transport in insulin-responsive cells.
Insulin receptor substrate 1 mediates the stimulatory effect of insulin on GLUT4 translocation in transfected rat adipose cells
Diabetes Branch, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892.
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J.-F. Tanti, T. Gremeaux, S. Grillo, V. Calleja, A. Klippel, L. T. Williams, E. Van Obberghen, and Y. Le Marchand-Brustel Overexpression of a Constitutively Active Form of Phosphatidylinositol 3-Kinase Is Sufficient to Promote Glut 4Translocation in Adipocytes J. Biol. Chem., October 11, 1996; 271(41): 25227 - 25232. [Abstract] [Full Text] [PDF]
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T. J. O'Neill, D. W. Rose, T. S. Pillay, K. Hotta, J. M. Olefsky, and T. A. Gustafson Interaction of a GRB-IR Splice Variant (a Human GRB10 Homolog) with the Insulin and Insulin-like Growth Factor I Receptors. EVIDENCE FOR A ROLE IN MITOGENIC SIGNALING J. Biol. Chem., September 13, 1996; 271(37): 22506 - 22513. [Abstract] [Full Text] [PDF]
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W. He, A. Craparo, Y. Zhu, T. J. O'Neill, L.-M. Wang, J. H. Pierce, and T. A. Gustafson Interaction of Insulin Receptor Substrate-2 (IRS-2) with the Insulin and Insulin-like Growth Factor I Receptors J. Biol. Chem., May 17, 1996; 271(20): 11641 - 11645. [Abstract] [Full Text] [PDF]
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R. A. Heller-Harrison, M. Morin, A. Guilherme, and M. P. Czech Insulin-mediated Targeting of Phosphatidylinositol 3-Kinase to GLUT4-containing Vesicles J. Biol. Chem., April 26, 1996; 271(17): 10200 - 10204. [Abstract] [Full Text] [PDF]
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T. C. Yeh, W. Ogawa, A. G. Danielsen, and R. A. Roth Characterization and Cloning of a 58/53-kDa Substrate of the Insulin Receptor Tyrosine Kinase J. Biol. Chem., February 9, 1996; 271(6): 2921 - 2928. [Abstract] [Full Text] [PDF]
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R. A. Heller-Harrison, M. Morin, and M. P. Czech Insulin Regulation of Membrane-associated Insulin Receptor Substrate 1 J. Biol. Chem., October 13, 1995; 270(41): 24442 - 24450. [Abstract] [Full Text] [PDF]
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A. G. Danielsen, F. Liu, Y. Hosomi, K. Shii, and R. A. Roth Activation of Protein Kinase Calpha Inhibits Signaling by Members of the Insulin Receptor Family J. Biol. Chem., September 15, 1995; 270(37): 21600 - 21605. [Abstract] [Full Text] [PDF]
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A. Kosaki, T. S. Pillay, L. Xu, and N. J. G. Webster The B Isoform of the Insulin Receptor Signals More Efficiently Than the A Isoform in HepG2 Cells J. Biol. Chem., September 1, 1995; 270(35): 20816 - 20823. [Abstract] [Full Text] [PDF]
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L. S. Argetsinger, G. W. Hsu, M. G. Myers Jr., N. Billestrup, M. F. White, and C. Carter-Su Growth Hormone, Interferon-[IMAGE], and Leukemia Inhibitory Factor Promoted Tyrosyl Phosphorylation of Insulin Receptor Substrate-1 J. Biol. Chem., June 16, 1995; 270(24): 14685 - 14692. [Abstract] [Full Text] [PDF]
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M. Fasshauer, J. Klein, K. Ueki, K. M. Kriauciunas, M. Benito, M. F. White, and C. R. Kahn Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes J. Biol. Chem., August 11, 2000; 275(33): 25494 - 25501. [Abstract] [Full Text] [PDF]
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L. V. Ravichandran, D. L. Esposito, J. Chen, and M. J. Quon Protein Kinase C-zeta Phosphorylates Insulin Receptor Substrate-1 and Impairs Its Ability to Activate Phosphatidylinositol 3-Kinase in Response to Insulin J. Biol. Chem., January 26, 2001; 276(5): 3543 - 3549. [Abstract] [Full Text] [PDF]
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A. R. Jacobs, D. LeRoith, and S. I. Taylor Insulin Receptor Substrate-1 Pleckstrin Homology and Phosphotyrosine-binding Domains Are Both Involved in Plasma Membrane Targeting J. Biol. Chem., October 26, 2001; 276(44): 40795 - 40802. [Abstract] [Full Text] [PDF]
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