Platelet-Derived Growth Factor Induces Multisite Phosphorylation of pp6Oc-src and Increases Its Protein-Tyrosine Kinase Activity

We have shown previously that pp69>-sc is a substrate for protein kinase C in vitro and in vivo and that the target of protein kinase C phosphorylation in mammalian pp6OcSrc is serine 12. We now demonstrate that in addition to tumor promoters, all activators of phosphatidylinositol turnover that we have tested in fibroblasts (platelet-derived growth factor, fibroblast growth factor, serum, vasopressin, sodium orthovanadate, and prostaglandin F2.) lead to the phosphorylation of pp60c-sr at serine 12. In addition to stimulating serine 12 phosphorylation in pp6Oc-"s, platelet-derived growth factor treatment of quiescent fibroblasts induces phosphorylation of one or two additional serine residues and one tyrosine residue within the N-terminal 16 kilodaltons of the enzyme and activates its immune complex protein-tyrosine kinase activity.

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