Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase

Midori Maekawa, Toshimasa Ishizaki, Shuken Boku, Naoki Watanabe, Akiko Fujita, Akihiro Iwamatsu, Takashi Obinata, Kazumasa Ohashi, Kensaku Mizuno, Shuh Narumiya

Research output: Contribution to journalArticlepeer-review

1171 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)895-898
Number of pages4
JournalScience
Volume285
Issue number5429
DOIs
Publication statusPublished - 1999 Aug 6

ASJC Scopus subject areas

  • General

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