p190RhoGAP has cellular RacGAP activity regulated by a polybasic region
p190RhoGAP has cellular RacGAP activity regulated by a polybasic region
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DOI：
10.1016/j.cellsig.2013.03.004
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发表时间：
2013-06-01
影响因子：
4.8
通讯作者：
Ligeti, Erzsebet
中科院分区：
文献类型：
--
作者：
Levay, Magdolna;Bartos, Balazs;Ligeti, Erzsebet
p190RhoGAP 是一种 GTP 酶激活蛋白 (GAP)，已知可通过激活 Rho 的内在 GTP 酶活性来降低 RhoGTP 水平，从而调节肌动蛋白细胞骨架动力学。尽管p190RhoGAP的GAP结构域在体外条件下刺激几个Rho家族成员（Rho、Rac、Cdc42）的内在GTP酶活性，但是p190RhoGAP通常被认为是细胞中RhoA的GAP。该蛋白的细胞 RacGAP 活性尚未得到直接证实。我们之前已经表明，p190RhoGAP 的体外 RacGAP 和 RhoGAP 活性是通过蛋白质的多碱基区域反向调节的。在这里，我们提供的证据表明 p190RhoGAP 在细胞中也对 Rac 显示出显着的 GAP 活性。 p190RhoGAP 的细胞 RacGAP 活性需要与 GAP 结构域相邻的完整多碱基区域，而 RhoGAP 活性被同一结构域抑制。我们的数据表明，通过其交替的 RacGAP 和 RhoGAP 活性，p190RhoGAP 在 Rac-Rho 拮抗作用中发挥着比之前认识到的更复杂的作用。 (C) 2013 Elsevier Inc. 保留所有权利。
p190RhoGAP is a GTPase-activating protein (GAP) known to regulate actin cytoskeleton dynamics by decreasing RhoGTP levels through activation of the intrinsic GTPase activity of Rho. Although the GAP domain of p190RhoGAP stimulates the intrinsic' GTPase activity of several Rho family members (Rho, Rac, Cdc42) under in vitro conditions, p190RhoGAP is generally regarded as a GAP for RhoA in the cell. The cellular RacGAP activity of the protein has not been proven directly. We have previously shown that the in vitro RacGAP and RhoGAP activity of p190RhoGAP was inversely regulated through a polybasic region of the protein. Here we provide evidence that p190RhoGAP shows remarkable GAP activity toward Rac also in the cell. The cellular RacGAP activity of p190RhoGAP requires an intact polybasic region adjacent to the GAP domain whereas the RhoGAP activity is inhibited by the same domain. Our data indicate that through its alternating RacGAP and RhoGAP activity, p190RhoGAP plays a more complex role in the Rac-Rho antagonism than it was realized earlier. (C) 2013 Elsevier Inc. All rights reserved.