Tyr 527 Is Phosphorylated in pp60 c- src : Implications for Regulation

The Rous sarcoma virus oncogene product, pp60 v- src , transforms cultured fibroblasts but its corresponding proto-oncogene product, pp60 c- src , does not. Both proteins are known to be protein-tyrosine kinases. Published results suggest that the kinase activity of pp60 c- src is inhibited relative to that of pp60 v- src , due perhaps to phosphorylation of a tyrosine in pp60 c- src that is not phosphorylated in pp60 v- src . In this study, it was observed that the tyrosine phosphorylated in pp60 c- src is Tyr 527 , six residues from the COOH-terminus of the protein. The region of pp60 c- src from residue 515 to the COOH-terminus, including Tyr 527 , has been replaced with a different sequence in pp60 v- src . Thus, the increase in transforming ability and kinase activity that occurred in the genesis of pp60 v- src may have resulted from the loss of a tyrosine involved in negative regulation.