Translocation of pp60c‐src to the cytoskeleton during platelet aggregation

The high amount of pp60c‐src in platelets has led to speculation that this kinase is responsible for tyrosine‐specific phosphorylation of cellular proteins during platelet activation by different agonists, and is, therefore, implicated in signal transduction of these cells. Unlike pp60v‐src, the association of which with the cytoskeleton appears to be a prerequisite for transformation, pp60c‐src is detergent‐soluble in fibroblasts overexpressing the c‐src gene, and its role in normal cellular function remains elusive. To gain a better understanding of the function of pp60c‐src we have investigated the subcellular distribution of pp60c‐src and its relationship to the cytoskeleton during platelet activation. Quantitative immunoblotting and immunoprecipitation have revealed that pp60c‐src is detergent‐soluble in resting platelets, while 40% of total platelet pp60c‐src becomes associated with the cytoskeletal fraction upon platelet activation. We have also shown that a small pool of pp60c‐src is associated with the membrane skeletal fraction which remains unchanged during the activation process. The interaction of pp60c‐src with cytoskeletal proteins strongly correlates with aggregation and is mediated by GPIIb/IIIa receptor‐fibrinogen binding. We suggest that the translocation of pp60c‐src to the cytoskeleton and its association with cytoskeletal proteins may regulate tyrosine phosphorylation in platelets.