Arthur W T, Petch L A, Burridge K
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599, USA.
Curr Biol. 2000 Jun 15;10(12):719-22. doi: 10.1016/s0960-9822(00)00537-6.
The Rho family GTPases Cdc42, Rac1 and RhoA control many of the changes in the actin cytoskeleton that are triggered when growth factor receptors and integrins bind their ligands [1] [2]. Rac1 and Cdc42 stimulate the formation of protrusive structures such as membrane ruffles, lamellipodia and filopodia. RhoA regulates contractility and assembly of actin stress fibers and focal adhesions. Although prolonged integrin engagement can stimulate RhoA [3] [4] [5], regulation of this GTPase by early integrin-mediated signals is poorly understood. Here we show that integrin engagement initially inactivates RhoA, in a c-Src-dependent manner, but has no effect on Cdc42 or Rac1 activity. Additionally, early integrin signaling induces activation and tyrosine phosphorylation of p190RhoGAP via a mechanism that requires c-Src. Dynamic modulation of RhoA activity appears to have a role in motility, as both inhibition and activation of RhoA hinder migration [6] [7] [8]. Transient suppression of RhoA by integrins may alleviate contractile forces that would otherwise impede protrusion at the leading edge of migrating cells.
Rho家族小G蛋白Cdc42、Rac1和RhoA控制着生长因子受体和整合素与其配体结合时引发的肌动蛋白细胞骨架的许多变化[1][2]。Rac1和Cdc42刺激突出结构的形成，如膜皱褶、片状伪足和丝状伪足。RhoA调节肌动蛋白应力纤维和粘着斑的收缩性和组装。尽管整合素的长时间结合可刺激RhoA[3][4][5]，但早期整合素介导的信号对这种小G蛋白的调节仍知之甚少。在这里，我们表明整合素的结合最初以c-Src依赖的方式使RhoA失活，但对Cdc42或Rac1活性没有影响。此外，早期整合素信号通过一种需要c-Src的机制诱导p190RhoGAP的激活和酪氨酸磷酸化。RhoA活性的动态调节似乎在运动中起作用，因为RhoA的抑制和激活都会阻碍迁移[6][7][8]。整合素对RhoA的短暂抑制可能减轻收缩力，否则这些收缩力会阻碍迁移细胞前缘的突出。
