Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase

• Midori Maekawa

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

• Toshimasa Ishizaki

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

• Shuken Boku

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

• Naoki Watanabe

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

• Akiko Fujita

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

• Akihiro Iwamatsu

  Central Laboratories for Key Technology, Kirin Brewery, Yokohama 236-0004, Japan.

• Takashi Obinata

  Department of Biology, Faculty of Science, Chiba University, Chiba 263-8522, Japan.

• Kazumasa Ohashi

  Biological Institute, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.

• Kensaku Mizuno

  Biological Institute, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.

• Shuh Narumiya

  Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.

抄録

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.

収録刊行物

• Science

  Science 285 (5429), 895-898, 1999-08-06

  American Association for the Advancement of Science (AAAS)

キーワード

• Multidisciplinary

詳細情報

• CRID: 1364233269644549632
• NII論文ID: 80011250806
• DOI: 10.1126/science.285.5429.895
• ISSN: 10959203
• ISSN: 00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.285.5429.895
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