Platelet-derived growth factor (PDGF) stimulated the tyroslne phosphorylation of the GTPase activating protein (GAP) In 3T3 cells and in CHO cells expressing wild-type PDGF receptors, but not in several CHO cell lines expressing mutant receptors defective in transmittlng mltogenic slgnals. Following PDGF treatment of cells, GAP physkally associated with the PDGF receptor and with Raf-1, phosphollpase c--y, and PI-3 kinase, suggestlng tftat PDGF Induced the formation of complexes of signaling molecules. The association of GAP with the PDGF receptor and the phosphorylation of GAP were mconstltuted in vitro using purified protein and in insect cells expressing murine PDGF receptor and human GAP However, in cells transformed by activated c-Ha-ras, which are defective in certain responses to PDGF, GAP failed to associate with the PDGF receptor or increase its phosphotymsine content in response to PDGF. The association of GAP with ligand-actfvated PDGF receptors may directly link PDGF and ras signaling pathways.