Redox-dependent downregulation of Rho by Rac
Redox-dependent downregulation of Rho by Rac
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DOI：
10.1038/ncb938
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发表时间：
2003-03-01
影响因子：
21.3
通讯作者：
Bar-Sagi, D
中科院分区：
文献类型：
--
作者：
Nimnual, AS;Taylor, LJ;Bar-Sagi, D
Rac和Rho GTP酶在细胞伸展和迁移过程中作为肌动蛋白细胞骨架重塑的关键调节因子发挥作用。在这里，我们表明，Rac介导的活性氧（ROS）的生产导致Rho活性下调。Rho活性的氧化还原依赖性降低是Rac诱导的膜皱褶形成和整合素介导的细胞铺展所必需的。ROS的产生与Rho的下调之间的联系途径包括抑制低分子量蛋白酪氨酸磷酸酶（LMW-PTP），然后增加其靶点p190 Rho-GAP的酪氨酸磷酸化和活化。我们的研究结果定义了一个新的机制耦合的细胞氧化还原状态的变化，以控制肌动蛋白细胞骨架重排的Rho GTPases。
Rac and Rho GTPases function as critical regulators of actin cytoskeleton remodelling during cell spreading and migration. Here we demonstrate that Rac-mediated reactive oxygen species (ROS) production results in the downregulation of Rho activity. The redox-dependent decrease in Rho activity is required for Rac-induced formation of membrane ruffles and integrin-mediated cell spreading. The pathway linking generation of ROS to downregulation of Rho involves inhibition of the low-molecular-weight protein tyrosine phosphatase (LMW-PTP) and then an increase in the tyrosine phosphorylation and activation of its target, p190Rho-GAP. Our findings define a novel mechanism for the coupling of changes in cellular redox state to the control of actin cytoskeleton rearrangements by Rho GTPases.