Translocation of pp60c-src from the plasma membrane to the cytosol after stimulation by platelet-derived growth factor.

The src family of protein-tyrosine kinases has long been implicated in signal transduction by growth factor receptors. In particular, pp60c-src, the product of the protooncogene c-src, has been shown to associated with the activated platelet-derived growth factor (PDGF) receptor. We demonstrate that, following stimulation of quiescent cells with PDGF, pp60c-src is translocated from the plasma membrane to the cytosol. This phenomenon was better defined utilizing an isolated plasma membrane system. The release of pp60c-src from the membrane in response to PDGF is accompanied by a 4-fold activation of its kinase activity and by phosphorylation at the amino terminus on serine/threonine residues as well as tyrosine residues. This amino-terminal phosphorylation appears to be responsible for a change in hydrophobicity of the pp60c-src molecule and hence for its release from the membrane. The kinase responsible for the serine/threonine phosphorylation and the concomitant release of pp60c-src has been identified as the cAMP-dependent protein kinase. Thus, PDGF stimulation activates at least two membrane-associated kinases (pp60c-src and cAMP-dependent protein kinase) very early in its signal transduction pathway.