The protein tyrosine kinase pp60c-src is activated upon platelet stimulation.
Stimulation of human platelets causes a dramatic increase in phosphorylation of various proteins at tyrosine residues. The abundance of protein tyrosine kinases of the src-family in platelets, particularly pp60c-src, suggests an important role of these kinases in response to stimulation events. We have shown that pp60c-src is activated on agonist-induced platelet stimulation with respect to its substrate affinity. This was accompanied by phosphorylation of pp60c-src at Ser-12, a residue which is phosphorylated by PKC. Inhibition of PKC with a specific inhibitor, Ro-31-8220, suppressed thrombin-induced translocation of pp60c-src to the cytoskeleton. On the basis of our data, we suggest that the cytoskeletal association of pp60c-src is dependent on phosphorylation of pp60c-src at Ser-12 by PKC. Phosphorylation at Ser-12 in the membrane-binding domain might be the signal that displaces pp60c-src from the plasma membrane and, accompanied with the increased substrate affinity, facilitates phosphorylation of putative substrates.
Liebenhoff
U
U
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
Greinacher
A
A
Presek
P
P
D001127:Arginine Vasopressin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007211:Indoles; D001127:Arginine Vasopressin; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220