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.
Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary.
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Horvath
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Muszbek
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Kellie
D001692:Biological Transport; D015153:Blotting, Western; D003599:Cytoskeleton / Q000378:metabolism*; D003902:Detergents; D006801:Humans; D017830:Octoxynol; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation; D011092:Polyethylene Glycols; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D003902:Detergents; D011092:Polyethylene Glycols; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D013917:Thrombin