mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation
mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation
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DOI：
10.1074/jbc.m107026200
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发表时间：
2001-10-19
影响因子：
4.8
通讯作者：
Tominaga, T
中科院分区：
文献类型：
--
作者：
Satoh, S;Tominaga, T
Rho同源蛋白mDia是一种Rho GT3效应蛋白，参与应激纤维形成、胞质分裂和血清应答因子的转录激活。虽然Rho的另一种效应物Rho相关激酶的功能已经得到了很好的证实，但对mDia的功能机制和下游靶点知之甚少。我们最近的Rho-mDia-Src-酪氨酸激酶通路的报告表明，mDia在细胞粘附周转中发挥重要作用。我们发现了一种新的mDia相互作用蛋白，它在细胞中广泛表达。新蛋白主要通过其Src同源3结构域与mDia的富含脯氨酸的区域结合，并且还通过其富含脯氨酸的结构域与Grb 2结合。该蛋白定位于细胞外周和膜皱褶处，并与mDia共定位。vSrc和mDia相互作用蛋白的共表达在焦点接触和vSrc的激活处诱导显著的形态学变化。此外，我们发现mDia相互作用蛋白在活性mDia 1诱导的应力纤维形成中起着重要作用。我们的研究结果表明，这种新的蛋白质调节肌动蛋白聚合和细胞粘附的Rho-mDia通路的下游部分的营业额通过与Grb 2和Src相互作用。
The formin homology protein mDia is a Rho GTPase effector protein that participates in stress fiber formation, cytokinesis, and transcriptional activation of the serum response factor. Although the function of another effector of Rho, Rho-associated kinase, is well established, relatively little is known about the functional mechanism and the downstream targets of mDia. Our recent report of a Rho-mDia-Src-tyrosine kinase pathway suggested an important role for mDia in cell adhesion turnover. We identified a new mDia-interacting protein which is expressed ubiquitously. The new protein mainly binds to the proline-rich region of mDia through its Src homology 3 domain and also binds to Grb2 through its proline-rich domain. The protein is localized at the cell periphery and membrane ruffles and co-localizes with mDia. Co-expression of vSrc and the mDia-interacting protein induces significant morphological changes at focal contacts and activation of vSrc. Furthermore, we found that the mDia-interacting protein plays an important role in stress fiber formation induced by active mDia1. Our results suggest that this new protein regulates actin polymerization and cell adhesion turnover in the downstream portion of the Rho-mDia pathway by interacting with Grb2 and Src.