RHO-STIMULATED CONTRACTILITY DRIVES THE FORMATION OF STRESS FIBERS AND FOCAL ADHESIONS

Activated rhoA, a ras-related GTP-binding protein, stimulates the appe arance 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 elucida ted. Many of the agents that activate rho (e.g., vasopressin, endothel in, lysophosphatidic acid) stimulate the contractility of smooth muscl e and other cells. We have investigated whether rho's induction of str ess fibers, focal adhesions, and tyrosine phosphorylation is the resul t of its stimulation of contractility. We demonstrate that stimulation of fibroblasts with lysophosphatidic acid, which activates rho, induc es myosin light chain phosphorylation. This precedes the formation of stress fibers and focal adhesions and is accompanied by increased cont ractility. Inhibition of contractility by several different mechanisms leads to inhibition of rho-induced stress fibers, focal adhesions, an d tyrosine phosphorylation. In addition, when contractility is inhibit ed, 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, dri ving the formation of stress fibers and focal adhesions and elevating tyrosine phosphorylation. A model is proposed to account for how contr actility could promote these events.