PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY IS REQUIRED FOR THE ACTIVATIONPROCESS OF FOCAL ADHESION KINASE BY PLATELET-DERIVED GROWTH-FACTOR

Platelet-derived growth factor (PDGF) is one of the agents which stimu late increase in phosphotyrosine content of focal adhesion kinase (FAK ) in cultured cells. In the present study we report that wortmannin, a highly specific and potent inhibitor of the catalytic subunit of mamm alian phosphatidylinositol (PI) 3-kinase, completely abolishes PDGF-BB -mediated increase in tyrosine phosphorylation of FAK in human umbilic al vein smooth muscle cells. Furthermore, analysis of the wild-type an d mutant human PDGF Preceptors stably expressed in porcine aortic endo thelial cells also demonstrates that the Y740/751F mutant receptor, wh ich cannot interact with PI 3-kinase due to the mutational alteration of its binding sites for PI 3-kinase, fails to increase FAK phosphoryl ation after PDGF-BB stimulation. These data suggest the requirement fo r PI 3-kinase activity in the activation process of FAK downstream of the PDGF receptor. (C) 1996 Academic Press, Inc.