RhoA and ROCK promote migration by limiting membrane protrusions
RhoA and ROCK promote migration by limiting membrane protrusions
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DOI：
10.1074/jbc.m211584200
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发表时间：
2003-04-11
影响因子：
4.8
通讯作者：
Burridge, K
中科院分区：
文献类型：
--
作者：
Worthylake, RA;Burridge, K
此前，我们及其他研究人员已经表明，RhoA和ROCK信号通路对于负向调节整合素介导的黏附以及迁移白细胞的尾部回缩是必需的。本研究继续对RhoA/ROCK调节整合素黏附的分子机制进行探究。我们发现抑制ROCK会上调整合素介导的黏附，同时伴有通过Pyk - 2和桩蛋白的磷酸酪氨酸信号增强以及不适当的膜突起。我们有证据表明抑制ROCK通过促进肌动蛋白细胞骨架的重塑来诱导整合素黏附。此外，我们发现ROCK通过一条涉及丝切蛋白的途径调节膜活性。抑制RhoA信号通路会导致多个相互竞争的片状伪足形成，从而破坏单核细胞的有效迁移。总之，我们的研究结果表明，RhoA/ROCK信号通路通过将整合素活性和膜突起限制在前沿来促进迁移。
Previously, we and others have shown that RhoA and ROCK signaling are required for negatively regulating integrin-mediated adhesion and for tail retraction of migrating leukocytes. This study continues our investigation into the molecular mechanisms underlying RhoA/ROCK-regulated integrin adhesion. We show that inhibition of ROCK up-regulates integrin-mediated adhesion, which is accompanied by both increased phosphotyrosine signaling through Pyk-2 and paxillin and inappropriate membrane protrusions. We provide evidence that inhibition of ROCK induces integrin adhesion by promoting remodeling of the actin cytoskeleton. Furthermore, we find that ROCK regulates membrane activity through a pathway involving cofilin. Inhibition of RhoA signaling allows the formation of multiple competing lamellipodia that disrupt productive migration of monocytes. Together, our results show that RhoA/ROCK signaling promotes migration by restricting integrin activity and membrane protrusions to the leading edge.