Abstract
In rabbit aortic vascular smooth muscle cells (VSMC) platelet-derived growth factor BB (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 (p125FAK) tyrosine phosphorylation, which was half-maximal and maximum at 1 and 2.5 ng/ml, respectively. Saliently, stimulation of p125FAK 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 p125FAK and paxillin tyrosine phosphorylation in human aortic VSMC. PDGF-BB caused no detectable disruption of the actin cytoskeleton in VSMC. PDGF-BB stimulated rabbit VSMC migration with a very similar concentration dependence to that for p125FAK and paxillin tyrosine phosphorylation. PDGF-BB was equally effective in stimulating p125FAK and paxillin tyrosine phosphorylation under conditions similar to those used for cell migration. In Swiss 3T3 fibroblasts, PDGF-BB and -AA stimulated p125FAK 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 p125FAK in the chemotactic response to PDGF-BB and suggest that the ability of PDGF-BB to trigger the p125FAK pathway may be dependent both upon cell type and receptor isotype expression.
Highlights
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*
PDGF-BB was effective in stimulating p125FAK and paxillin tyrosine phosphorylation under conditions similar to those used for cell migration
We report that in aortic vascular smooth muscle cells (VSMC) PDGF-BB stimulates a rapid tyrosine phosphorylation of p125FAK which is sustained at high concentrations of the growth factor and is mediated via the f3-receptor
Summary
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*. About the components or intracellular signaling pathways which mediate the effects ofPDGF-BB on cell migration and locomotion in VSMC [22] It is likely, that these processes are crucially dependent on interactions involving extracellular matrix components, integrins, the cyhomodimer; PDGF-BB, platelet-derived growth factor BB homodimer; PDGF-R, platelet-derived growth factor receptor; PAGE, polyacrylamide gel electrophoresis; FITC, fluorescein isothiocyante. We present evidence that the ability ofPDGF-BB to cause p125FAK tyrosine phosphorylation in both VSMC and in Swiss 3T3 cells selectively correlates with its ability to promote cell migration
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