Rho-stimulated contractility drives the formation of stress fibers and focal adhesions.
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.
Chrzanowska-Wodnicka
M
M
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599, USA.
Burridge
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016475:3T3 Cells / Q000166:cytology; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000032:analysis; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002448:Cell Adhesion / Q000502:physiology*; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007211:Indoles; D019012:Integrin beta1 / Q000032:analysis / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000378:metabolism; D009218:Myosins / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D000199:Actins; D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D019012:Integrin beta1; D007546:Isoquinolines; D008246:Lysophospholipids; D018994:Myosin Light Chains; D010879:Piperazines; C063769:KT 5926; C004717:diacetylmonoxime; D014443:Tyrosine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009218:Myosins; D020742:rhoA GTP-Binding Protein; D003931:Diacetyl