RhoE binds to ROCK I and inhibits downstream signaling
RhoE binds to ROCK I and inhibits downstream signaling
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DOI：
10.1128/mcb.23.12.4219-4229.2003
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发表时间：
2003-06-01
影响因子：
5.3
通讯作者：
Ridley, AJ
中科院分区：
文献类型：
--
作者：
Riento, K;Guasch, RM;Ridley, AJ
RhoE属于Rho GTdR家族，其成员控制肌动蛋白细胞骨架动力学。RhoE在多种细胞类型中诱导应力纤维分解，而RhoA刺激应力纤维组装。RhoE和RhoA序列的相似性表明RhoE可能与RhoA竞争与其靶标的相互作用。在这里，我们表明RhoE结合ROCK I，但没有测试的其他RhoA靶标。RhoE与ROCK I的相互作用通过内源性蛋白质的共免疫沉淀来证实，并且这两种蛋白质在COS-7细胞中共定位在trans-Golgi网络上。虽然RhoE和RhoA不能同时结合ROCK I，但RhoE在远离羧基末端RhoA结合位点的位点处结合到包含激酶结构域的ROCK I的氨基末端区域。RhoE的过表达抑制ROCK I诱导的应力纤维形成和ROCK I靶肌球蛋白轻链磷酸酶的磷酸化。这些数据表明RhoE通过直接结合ROCK I并抑制其磷酸化下游靶标来诱导应力纤维分解。
RhoE belongs to the Rho GTPase family, the members of which control actin cytoskeletal dynamics. RhoE induces stress fiber disassembly in a variety of cell types, whereas RhoA stimulates stress fiber assembly. The similarity of RhoE and RhoA sequences suggested that RhoE might compete with RhoA for interaction with its targets. Here, we show that RhoE binds ROCK I but none of the other RhoA targets tested. The interaction of RhoE with ROCK I was confirmed by coimmunoprecipitation of the endogenous proteins, and the two proteins colocalized on the trans-Golgi network in COS-7 cells. Although RhoE and RhoA were not able to bind ROCK I simultaneously, RhoE bound to the amino-terminal region of ROCK I encompassing the kinase domain, at a site distant from the carboxy-terminal RhoA-binding site. Overexpression of RhoE inhibited ROCK I-induced stress fiber formation and phosphorylation of the ROCK I target myosin light chain phosphatase. These data suggest that RhoE induces stress fiber disassembly by directly binding ROCK I and inhibiting it from phosphorylating downstream targets.