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信号素4D/丛状蛋白-B1介导的R-Ras GAP活性通过调节β1整合素活性抑制细胞迁移。

Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating beta(1) integrin activity.

作者信息

Oinuma Izumi, Katoh Hironori, Negishi Manabu

机构信息

Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

出版信息

J Cell Biol. 2006 May 22;173(4):601-13. doi: 10.1083/jcb.200508204. Epub 2006 May 15.

DOI:10.1083/jcb.200508204
PMID:16702230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2063868/
Abstract

Plexins are cell surface receptors for semaphorins and regulate cell migration in many cell types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) for R-Ras, a member of Ras family GTPases implicated in regulation of integrin activity and cell migration. We characterized the role of R-Ras downstream of Sema4D/Plexin-B1 in cell migration. Activation of Plexin-B1 by Sema4D suppressed the ECM-dependent R-Ras activation, R-Ras-mediated phosphatydylinositol 3-kinase activation, and beta(1) integrin activation through its R-Ras GAP domain, leading to inhibition of cell migration. In addition, inactivation of R-Ras by overexpression of the R-Ras-specific GAP or knockdown of R-Ras by RNA interference was sufficient for suppressing beta(1) integrin activation and cell migration in response to the ECM stimulation. Thus, we conclude that R-Ras activity is critical for ECM-mediated beta(1) integrin activation and cell migration and that inactivation of R-Ras by Sema4D/Plexin-B1-mediated R-Ras GAP activity controls cell migration by modulating the activity of beta(1) integrins.

摘要

丛状蛋白是信号素的细胞表面受体，可调节多种细胞类型的细胞迁移。我们最近报道，信号素4D（Sema4D）受体丛状蛋白-B1作为R-Ras的GTP酶激活蛋白（GAP）发挥作用，R-Ras是Ras家族GTP酶的成员之一，参与整合素活性调节和细胞迁移。我们对Sema4D/丛状蛋白-B1下游的R-Ras在细胞迁移中的作用进行了表征。Sema4D对丛状蛋白-B1的激活通过其R-Ras GAP结构域抑制了依赖于细胞外基质（ECM）的R-Ras激活、R-Ras介导的磷脂酰肌醇3激酶激活以及β1整合素激活，从而导致细胞迁移受到抑制。此外，通过R-Ras特异性GAP的过表达使R-Ras失活或通过RNA干扰敲低R-Ras，足以抑制ECM刺激引起的β1整合素激活和细胞迁移。因此，我们得出结论，R-Ras活性对于ECM介导的β1整合素激活和细胞迁移至关重要，并且Sema4D/丛状蛋白-B1介导的R-Ras GAP活性使R-Ras失活，通过调节β1整合素的活性来控制细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/19f75562127f/jcb1730601f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/0b72188bac28/jcb1730601f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/058dc825038d/jcb1730601f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/b42c413be731/jcb1730601f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/6bfb94c3be6c/jcb1730601f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/5fb6efe4bb3b/jcb1730601f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/0f9eb985433d/jcb1730601f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/f355cfabdafe/jcb1730601f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/d3584a7444c9/jcb1730601f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/9dc4eb959fc3/jcb1730601f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/19f75562127f/jcb1730601f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/0b72188bac28/jcb1730601f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/058dc825038d/jcb1730601f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/b42c413be731/jcb1730601f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/6bfb94c3be6c/jcb1730601f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/5fb6efe4bb3b/jcb1730601f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/0f9eb985433d/jcb1730601f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/f355cfabdafe/jcb1730601f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/d3584a7444c9/jcb1730601f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/9dc4eb959fc3/jcb1730601f09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b8/2063868/19f75562127f/jcb1730601f10.jpg

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