AbstractBoth platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce autogenesis in normal rat kidney (NRK) fibroblasts transformed by the polyoma virus middle T (pmt) oncogene. In unstimulated pmt-NRK cells phosphatidylinositol 3-kinase forms a complex with the middle T protein and pp60c-src. PDGF treatment causes a release of phosphatidylinositol 3-kinase activity from the complex and a simultaneous increase in activity associated with the PDGF receptor. In contrast after treatment with EGF the majority of phosphatidylinositol 3-kinase activity remains associated with the middle T-pp60c-srccomplex. Proliferation of NRK fibroblasts transformed by the v-src oncogene is already maximal, and no further stimulation is observed with either PDGF or EGF. Neither growth factor induces dissociation of the complex between phosphatidylinositol 3-kinase and pp60v-src. These observations suggest that the complex between phosphatidylinositol 3-kinase, the middle T protein and pp60c-srcis dissociable, and that phosphatidylinositol 3-kinase plays different roles in mitogenic signal transduction by the PDGF and EGF receptors.