Chrzanowska-Wodnicka M, Burridge K
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599, USA.
J Cell Biol. 1996 Jun;133(6):1403-15. doi: 10.1083/jcb.133.6.1403.
Activated rhoA, a ras-related GTP-binding protein, stimulates the appearance of stress fibers, focal adhesions, and tyrosine phosphorylation in quiescent cells (Ridley, A.J., and A. Hall, 1992. Cell. 70:389-399). The pathway by which rho triggers these events has not been elucidated. Many of the agents that activate rho (e.g., vasopressin, endothelin, lysophosphatidic acid) stimulate the contractility of smooth muscle and other cells. We have investigated whether rho's induction of stress fibers, focal adhesions, and tyrosine phosphorylation is the result of its stimulation of contractility. We demonstrate that stimulation of fibroblasts with lysophosphatidic acid, which activates rho, induces myosin light chain phosphorylation. This precedes the formation of stress fibers and focal adhesions and is accompanied by increased contractility. Inhibition of contractility by several different mechanisms leads to inhibition of rho-induced stress fibers, focal adhesions, and tyrosine phosphorylation. In addition, when contractility is inhibited, integrins disperse from focal adhesions as stress fibers and focal adhesions disassemble. Conversely, upon stimulation of contractility, diffusely distributed integrins are aggregated into focal adhesions. These results suggest that activated rho stimulates contractility, driving the formation of stress fibers and focal adhesions and elevating tyrosine phosphorylation. A model is proposed to account for how contractility could promote these events.
活化的RhoA是一种与Ras相关的GTP结合蛋白，可刺激静止细胞中应力纤维、粘着斑和酪氨酸磷酸化的出现（Ridley，A.J.和A. Hall，1992年。《细胞》。70:389 - 399）。Rho触发这些事件的途径尚未阐明。许多激活Rho的因子（如血管加压素、内皮素、溶血磷脂酸）可刺激平滑肌和其他细胞的收缩性。我们研究了Rho诱导应力纤维、粘着斑和酪氨酸磷酸化是否是其刺激收缩性的结果。我们证明，用激活Rho的溶血磷脂酸刺激成纤维细胞会诱导肌球蛋白轻链磷酸化。这先于应力纤维和粘着斑的形成，并伴随着收缩性增加。通过几种不同机制抑制收缩性会导致抑制Rho诱导的应力纤维、粘着斑和酪氨酸磷酸化。此外，当收缩性受到抑制时，随着应力纤维和粘着斑的解体，整合素从粘着斑中分散。相反，在刺激收缩性时，分散分布的整合素会聚集形成粘着斑。这些结果表明，活化的Rho刺激收缩性，驱动应力纤维和粘着斑的形成并提高酪氨酸磷酸化。提出了一个模型来解释收缩性如何促进这些事件。
