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

我们首次报道了SHC的存在，它可以转化人类血小板中的NIH/3T3细胞。此外，我们发现在血小板中酪氨酸在血小板生成素的刺激下发生磷酸化。酪氨酸磷酸化后，SHC与另一种SH2/SH3适配蛋白Grb2相关。我们也报道了在剪切诱导的血小板聚集（SIPA）过程中，许多蛋白质在血小板中被酪氨酸磷酸化。我们也报道了血小板中有STAT3、STAT5、c-Cbl、Vav和Crkl，它们在血小板生成素刺激的正常人血小板中都被酪氨酸磷酸化。事实上，Crkl被认为是Bcr-Abl激酶的特异性底物，而Bcr-Abl激酶被认为与慢性髓性白血病（CML）的发病机制有关。然而，我们的发现表明，Bcr-Abl以外的激酶可以磷酸化酪氨酸残基上的Crkl，并提出了Crkl可能参与血小板生成素信号传导的可能性。由于血小板生成素对巨核生成至关重要，这也表明Crkl参与了巨核生成。总之，我们发现人类血小板中存在几种迄今尚未确定的蛋白质，它们可能参与血小板生成素的信号传导。

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.