p120 catenin regulates the actin cytoskeleton via Rho family GTPases.
p120 catenin regulates the actin cytoskeleton via Rho family GTPases.
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DOI：
10.1083/jcb.150.3.567
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发表时间：
2000-08-07
期刊：
影响因子：
--
通讯作者：
Kreft B
中科院分区：
文献类型：
--
作者：
Noren NK;Liu BP;Burridge K;Kreft B
钙粘蛋白是钙依赖性粘附分子，负责建立紧密的细胞-细胞接触。p120连环蛋白（p120 ctn）结合到质膜区域中的钙粘蛋白的胞质结构域，其涉及调节细胞运动性。先前已经表明，p120 ctn的过表达诱导成纤维细胞中的树突状形态（Reynolds，A.B.，J.丹尼尔，Y. Mo，J. Wu和Z.张某1996. Exp. Cell Res. 225：328-337）。我们在这里表明，这种表型是抑制共表达的钙粘蛋白的结构，包含质膜区域，但不是由结构缺乏这个域。p120 ctn的过表达破坏应力纤维和局灶性粘连，并导致RhoA活性降低。p120 ctn诱导的表型被显性负性Cdc 42和Rac 1以及组成性活性Rho激酶阻断，但被显性负性RhoA增强。p120 ctn过表达可增加内源性Cdc 42和Rac 1的活性。探索p120 ctn如何调节Rho家族GTP酶，我们发现p120 ctn结合Rho家族交换因子Vav 2。p120 ctn的行为表明，它是细胞间连接和细胞运动机制之间相互作用的载体。我们提出了一个模型，其中p120 ctn可以在钙粘蛋白结合状态和细胞质池之间穿梭，在细胞质池中它可以与Rho家族GTPases的调节因子相互作用。干扰细胞-细胞连接的因素，如p120 ctn的细胞质池增加，预计会降低RhoA活性，但提高活性Rac 1和Cdc 42，从而促进细胞迁移。
Cadherins are calcium-dependent adhesion molecules responsible for the establishment of tight cell–cell contacts. p120 catenin (p120ctn) binds to the cytoplasmic domain of cadherins in the juxtamembrane region, which has been implicated in regulating cell motility. It has previously been shown that overexpression of p120ctn induces a dendritic morphology in fibroblasts (Reynolds, A.B., J. Daniel, Y. Mo, J. Wu, and Z. Zhang. 1996. Exp. Cell Res. 225:328–337.). We show here that this phenotype is suppressed by coexpression of cadherin constructs that contain the juxtamembrane region, but not by constructs lacking this domain. Overexpression of p120ctn disrupts stress fibers and focal adhesions and results in a decrease in RhoA activity. The p120ctn-induced phenotype is blocked by dominant negative Cdc42 and Rac1 and by constitutively active Rho-kinase, but is enhanced by dominant negative RhoA. p120ctn overexpression increased the activity of endogenous Cdc42 and Rac1. Exploring how p120ctn may regulate Rho family GTPases, we find that p120ctn binds the Rho family exchange factor Vav2. The behavior of p120ctn suggests that it is a vehicle for cross-talk between cell–cell junctions and the motile machinery of cells. We propose a model in which p120ctn can shuttle between a cadherin-bound state and a cytoplasmic pool in which it can interact with regulators of Rho family GTPases. Factors that perturb cell–cell junctions, such that the cytoplasmic pool of p120ctn is increased, are predicted to decrease RhoA activity but to elevate active Rac1 and Cdc42, thereby promoting cell migration.
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
4.8
作者：
BAGRODIA, S;TAYLOR, SJ;CERIONE, RA
通讯作者：
CERIONE, RA