RT Journal Article
SR Electronic
T1 Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase
JF Science
JO Science
FD American Association for the Advancement of Science
SP 895
OP 898
DO 10.1126/science.285.5429.895
VO 285
IS 5429
A1 Maekawa, Midori
A1 Ishizaki, Toshimasa
A1 Boku, Shuken
A1 Watanabe, Naoki
A1 Fujita, Akiko
A1 Iwamatsu, Akihiro
A1 Obinata, Takashi
A1 Ohashi, Kazumasa
A1 Mizuno, Kensaku
A1 Narumiya, Shuh
YR 1999
UL http://science.sciencemag.org/content/285/5429/895.abstract
AB The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid–induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632–sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.