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.
Walker
F
F
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
deBlaquiere
J
J
Burgess
A W
AW
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020574:Proto-Oncogene Proteins c-sis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D006133:Growth Substances; D009227:Myristic Acids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D019814:Myristic Acid; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D010751:Phosphopyruvate Hydratase