Hamasaki K, Mimura T, Morino N, Furuya H, Nakamoto T, Aizawa S, Morimoto C, Yazaki Y, Hirai H, Nojima Y
Third Department of Internal Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1996 May 15;222(2):338-43. doi: 10.1006/bbrc.1996.0745.
A novel signaling molecule p130Cas has been shown to undergo tyrosine phosphorylation in response to integrin-mediated cell adhesion. In this study, we have attempted to identify kinases that mediate Cas phosphorylation in integrin signaling by examining various mutant cell lines that do not express either p125FAK, c-Scr, c-Fyn or c-Abl. We found that deficiency of c-Src but not of other kinases completely abrogated integrin-mediated Cas phosphorylation. Importantly, paxillin phosphorylation was not compromised in each mutant cell line examined. These results suggest that c-Src primarily mediates adhesion-dependent Cas phosphorylation. As for paxillin phosphorylation, there may exist substantial redundancy amongst multiple kinases. Finally, adhesion-induced Cas phosphorylation resulted in its association with c-Crk adapter protein via the Crk-SH2 domain. Thus, Cas plays a role in the transmission of integrin-initiated signals through tyrosine phosphorylation and subsequent binding to c-Crk.
一种新型信号分子p130Cas已被证明在整合素介导的细胞黏附反应中会发生酪氨酸磷酸化。在本研究中，我们试图通过检测不表达p125FAK、c-Scr、c-Fyn或c-Abl的各种突变细胞系，来鉴定整合素信号传导中介导Cas磷酸化的激酶。我们发现，c-Src的缺失而非其他激酶的缺失完全消除了整合素介导的Cas磷酸化。重要的是，在所检测的每个突变细胞系中，桩蛋白磷酸化并未受到影响。这些结果表明，c-Src主要介导黏附依赖性Cas磷酸化。至于桩蛋白磷酸化，多种激酶之间可能存在大量冗余。最后，黏附诱导的Cas磷酸化导致其通过Crk-SH2结构域与c-Crk衔接蛋白结合。因此，Cas通过酪氨酸磷酸化以及随后与c-Crk结合，在整合素起始信号的传递中发挥作用。
