Platelet activation leads to increased c-src kinase activity and association of c-src with an 85-kDa tyrosine phosphoprotein.
We have used platelets as a model system to study the function of c-src in signal transduction and cell adhesion. Numerous proteins were found to be phosphorylated on tyrosine in response to thrombin-induced platelet activation and aggregation. Two phases of phosphorylation were observed, with the second phase, but not the first, being inhibited by blocking platelet aggregation with an Arg-Gly-Asp-Ser tetrapeptide. As a first step towards identifying those proteins phosphorylated on tyrosine and to determine the specific role of p60src during platelet activation, we looked for changes in p60src kinase activity and for associations of p60src with other tyrosine phosphoproteins. The data presented here demonstrate an increase in p60src kinase activity within 1 min of thrombin-induced activation. Furthermore, p60src transiently associates with a tyrosine phosphoprotein during platelet activation and aggregation. This tyrosine phosphoprotein, p80/85, is a previously characterized cytoskeletal substrate for v-src in transformed cells. The data presented here suggest a model in which p60src functions in platelets to link upstream events, such as cell-surface adhesive interactions, with changes in platelet shape and cytoskeletal organization.
D000595:Amino Acid Sequence; D000906:Antibodies; D001792:Blood Platelets / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D016391:Genes, src; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000097:blood* / Q000302:isolation & purification; D019000:Phosphotyrosine; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000097:blood*; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000906:Antibodies; D009842:Oligopeptides; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)