PHOSPHATIDYLINOSITOL-3-KINASE IS A NONTYROSINE PHOSPHORYLATED MEMBER OF THE INSULIN-RECEPTOR SIGNALING COMPLEX

In rat HTC cells expressing a large number of human insulin receptors, insulin stimulated phosphatidylinositol-3-kinase (PI-3-kinase) activity. This activity was more effectively immunoprecipitated with anti-phosphotyrosine antibody (α-PY) than with anti-insulin receptor antibody (α-IR), suggesting that PI-3-kinase was not directly associated with the insulin receptor. α-PY immunoprecipitable PI-3-kinase activity, which was regulated by insulin, corresponded to a small pool of the total cellular PI-3-kinase activity. PI-3-kinase was not directly tyrosine phosphorylated by insulin treatment. A comparison of both catalytic activity and content of PI-3-kinase in α-PY immunoprecipitates indicated that after insulin treatment PI-3-kinase activity was enhanced by its association with tyrosine phosphorylated proteins. These studies suggest therefore that PI-3-kinase is a non-tyrosine phosphorylated member of the insulin receptor signalling complex. © 1992.