Insulin activation of mitogen-activated protein (MAP) kinase and AKT is phosphatidylinositol 3-kinase-dependent in rat adipocytes

To explore the mechanism of MAP kinase activation in adipocytes, we examine d the possible involvement of several candidate signaling proteins, MAP kin ase activity was markedly increased 2-4 min after treatment with insulin an d declined to basal levels after 20 min, The insulin-dependent tyrosine pho sphorylation of IRS-1 in the internal membrane and its association with pho sphatidylinositol 3 (PI3) kinase preceded MAP kinase activation. There was little or no tyrosine phosphorylation of She or association of Grb2 with Sh e or IRS-1. Specific PI3 kinase inhibitors blocked the insulin-mediated act ivation of MAP kinase. They also decreased the activation of MAP kinase by PMA and EGF but to a much lesser extent, Insulin induced phosphorylation of AKT on serine/threonine residues, and its effect could be blocked by PI3 k inase inhibitors. These results suggest that the insulin-dependent activati on of MAP kinase in adipocytes is mediated by the IRS-1/PI3 kinase pathway but not by the Shc/Grb2/SOS pathway. (C) 2000 Academic Press.