IRS-1 IS A COMMON ELEMENT IN INSULIN AND INSULIN-LIKE GROWTH FACTOR-I SIGNALING TO THE PHOSPHATIDYLINOSITOL 3'-KINASE

IRS-1 is a unique cytosolic protein that becomes tyrosine phosphorylated during insulin stimulation of intact cells and immediately associates with the phosphatidylinositol 3'-kinase (PtdIns 3'-kinase). The insulin-like growth factor-I (IGF-I) receptor also mediated the tyrosine phosphorylation of IRS-1 and increased the amount of Ptdlns 3'-kinase activity bound to IRS-1 in Chinese hamster ovary cells. Purified insulin receptor and IGF-1 receptor phosphorylated recombinant baculovirus-produced IRS-1 on similar sites in vitro, and phosphorylated baculovirus-produced IRS-1 bound Ptdlns 3'-kinase activity from lysates of quiescent cells. Treatment of cells with IGF-1 activated the PtdIns 3'-kinase, suggesting that IGF-1 activates the Ptdlns 3'-kinase through IRS-1 binding to p85 in a manner similar to insulin. Chinese hamster ovary cells overexpressing IRS-1 demonstrated increased tyrosine phosphorylation of IRS-1, and more PtdIns 3'-kinase activity associated with IRS-1 in these cells. These data demonstrate that IRS-1 is a common element for signal transmission by the IGF-I and insulin receptors.