Investigations on the new functions of SHC,Grb2, paxillin, Nck, Csk, PTPase 1C, PTPase 1D.

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We have reported for the first time the presence of SHC,which transforms cells like NIH/3T3, in human platelets. Further, we have found that this becomes tyrosine phosphorylated in platelets, stimulated by thrombopoietin. Upon tyrosine phosphorylation, SHC becomes associated with Grb2, another SH2/SH3 adapter protein. We also reported that numerous proteins become tyrosine phosphorylated in platelets during shear-induced platelet aggregation (SIPA). We have also reported that platelets have STAT3, STAT5, c-Cbl, Vav and Crkl, all of them become tyrosine phosphorylated in thrombopoietin-stimulated normal human platelets. Indeed, Crkl was thought to be a specific substrate for the Bcr-Abl kinase, which is believed to contribute to the pathogenesis of chronic myelogenous leukemia (CML). However, our finding indicates that kinases other than Bcr-Abl can phosphorylate Crkl on tyrosine residues and raises a possibility that Crkl may be involved in the signaling by thrombopoietin. Since thrombopoietin is essential for megakaryopoiesis, this also suggests that Crkl is involved in megakaryopoiesis. In conclusion, we have found that several proteins, hitherto unidentified, are present in human platelets, and that they may be involved in signaling by thrombopoietin.