Irs-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3′-kinase

IRS-l is a unique cytosolic protein that becomes tyrosine phosphor-ylated during insulin stimulation of intact cells and immediately associates with the phosphatidylinositol 3′-kinase (Ptdlns 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-I receptor phosphoryiated recombinant baculovirus-produced IRS-1 on similar sites in vitro, and phosphoryiated baculovirus-produced IRS-1 bound Ptdlns 3′-kinase activity from lysates of quiescent cells. Treatment of cells with IGF-I activated the Ptdlns 3′-kinase, suggesting that IGF-I 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 Ptdlns 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.