DIFFERENTIAL-EFFECTS OF PLATELET-DERIVED GROWTH-FACTOR BB ON P125 FOCAL ADHESION KINASE AND PAXILLIN TYROSINE PHOSPHORYLATION AND ON CELL-MIGRATION IN RABBIT AORTIC VASCULAR SMOOTH-MUSCLE CELLS AND SWISS 3T3 FIBROBLASTS

In rabbit aortic vascular smooth muscle cells (VSMC) platelet derived growth factor BE (PDGF-BB) stimulated the tyrosine phosphorylation of phospholipase C-gamma, p120 GTPase-activating protein, and the p85 alpha subunit of phosphatidylinositol 3'-kinase only at high concentrations (5-25 ng/ml), In contrast, PDGF-BB induced a rapid and concentration-dependent increase in p125 focal adhesion kinase (p125(FAK)) tyrosine phosphorylation, which was half-maximal and maximum at 1 and 2.5 ng/ml, respectively, Saliently, stimulation of p125(FAK) tyrosine phosphorylation was sustained at up to 100 ng/ml PDGF-BB and for prolonged times of treatment, With similar concentration dependence, PDGF-BB stimulated the tyrosine phosphorylation of the 68-kDa focal adhesion-associated protein, paxillin, PDGF-BB also induced p125(FAK) and paxillin tyrosine phosphorylation in human aortic VSMC, PDGF-EB caused no detectable disruption of the actin cytoskeleton in VSMC, PDGF-EB stimulated rabbit VSMC migration with a very similar concentration dependence to that for p125(FAK) and paxillin tyrosine phosphorylation, PDGF-BB was equally effective in stimulating p125(FAK) and paxillin tyrosine phosphorylation under conditions similar to those used for cell migration, In Swiss 3T3 fibroblasts, PDGF-BB and -AA stimulated p125(FAK) tyrosine phosphorylation and cell migration only at low concentrations, and stimulation was abolished at 10-25 ng/ml, PDGF-AA failed to stimulate tyrosine phosphorylation, mitogenesis, and chemotaxis in rabbit VSMC, and immunoblot analysis showed that rabbit VSMC expressed PDGF beta-receptors but no alpha-receptors. These results implicate p125(FAK) in the chemotactic response to PDGF-BB and suggest that the ability of PDGF-BB to trigger the p125(FAK) pathway may be dependent both upon cell type and receptor isotype expression.