Association of insulin receptor substrate-1 with integrins.
Insulin stimulation was found to promote association of the alpha v beta 3 integrin (a vitronectin receptor) with insulin receptor substrate-1 (IRS-1), an intracellular protein that mediates insulin signaling by binding other signaling molecules, including growth factor receptor-bound protein 2 (Grb2) and phosphatidylinositol-3' kinase. Insulin-treated cells expressing the alpha v beta 3 integrin showed 2.5 times more DNA synthesis when plated on vitronectin than on other substrates, whereas cells expressing another vitronectin receptor, alpha v beta 5, did not show this difference. The association between integrin and IRS-1 may be a mechanism for the synergistic action of growth factor and extracellular matrix receptors.
Vuori
K
K
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
Ruoslahti
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003094:Collagen; D004247:DNA / Q000096:biosynthesis; D006023:Glycoproteins; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D019030:Receptors, Vitronectin; D014162:Transfection; D014407:Tumor Cells, Cultured; D019096:Vitronectin
D006023:Glycoproteins; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D016023:Integrins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D019096:Vitronectin; D003094:Collagen; D004247:DNA; D011972:Receptor, Insulin