Differential mobilization of tyrosine kinases in human platelets stimulated with thrombin or thrombin receptor agonist peptide.

Both thrombin and thrombin receptor agonist peptide (TRAP) activated p72syk and p60c-src with similar magnitudes. Both thrombin and TRAP induced translocation of p60c-src and p54/58lyn to cytoskeleton in an aggregation-dependent manner. Thrombin also induced cytoskeletal association of p72syk, but independent of platelet aggregation. Furthermore, p72syk associated with cytoskeleton underwent marked proteolysis, which was partially dependent upon calpain activation. In contrast, TRAP, even at concentrations as high as 100 mu M, did not induce p72syk translocation to cytoskeleton. Our findings suggest that cytoskeletal translocation of p72syk induced by thrombin is governed by a mechanism distinct from those of p60c-src and p54/58lyn translocation. It is also suggested that p72syk translocation induced by thrombin requires additional signal(s) other than that mediated by the recently-cloned thrombin receptor that couples with GTP-binding proteins and interacts with TRAP.