Nimnual Anjaruwee S, Taylor Laura J, Bar-Sagi Dafna
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Nat Cell Biol. 2003 Mar;5(3):236-41. doi: 10.1038/ncb938.
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.
Rac和Rho GTP酶在细胞铺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。我们在此证明，Rac介导的活性氧（ROS）产生会导致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。将ROS生成与Rho下调联系起来的途径涉及对低分子量蛋白酪氨酸磷酸酶（LMW-PTP）的抑制，随后其靶标p190Rho-GAP的酪氨酸磷酸化和激活增加。我们的研究结果定义了一种新机制，将细胞氧化还原状态的变化与Rho GTP酶对肌动蛋白细胞骨架重排的控制联系起来。
