Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 1996 Jun;133(6):1403-15
Date
06/01/1996Pubmed ID
8682874Pubmed Central ID
PMC2120895DOI
10.1083/jcb.133.6.1403Scopus ID
2-s2.0-0029995797 (requires institutional sign-in at Scopus site) 1503 CitationsAbstract
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.
Author List
Chrzanowska-Wodnicka M, Burridge KAuthor
Magdalena Chrzanowska PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine3T3 Cells
Actin Cytoskeleton
Actins
Alkaloids
Animals
Carbazoles
Cell Adhesion
Diacetyl
Enzyme Inhibitors
Fibroblasts
GTP-Binding Proteins
Indoles
Integrin beta1
Isoquinolines
Lysophospholipids
Mice
Mice, Inbred BALB C
Muscle Contraction
Myosin Light Chains
Myosins
Phosphorylation
Piperazines
Protein Kinase C
Rats
Tyrosine
rhoA GTP-Binding Protein
