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Science 6 August 1999:
Vol. 285. no. 5429, pp. 895 - 898
DOI: 10.1126/science.285.5429.895
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Reports

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

Midori Maekawa, 1 Toshimasa Ishizaki, 1 Shuken Boku, 1 Naoki Watanabe, 1 Akiko Fujita, 1 Akihiro Iwamatsu, 2 Takashi Obinata, 3 Kazumasa Ohashi, 4 Kensaku Mizuno, 4 Shuh Narumiya 1*

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.

1 Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.
2 Central Laboratories for Key Technology, Kirin Brewery, Yokohama 236-0004, Japan.
3 Department of Biology, Faculty of Science, Chiba University, Chiba 263-8522, Japan.
4 Biological Institute, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
*   To whom correspondence should be addressed. E-mail: snaru{at}mfour.med.kyoto-u.ac.jp

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   Abstract »    Full Text »    PDF »
Attenuation of Endotoxin-Induced Acute Lung Injury by the Rho-Associated Kinase Inhibitor, Y-27632.
S. Tasaka, H. Koh, W. Yamada, M. Shimizu, Y. Ogawa, N. Hasegawa, K. Yamaguchi, Y. Ishii, S. E. Richer, C. M. Doerschuk, et al. (2005)
Am. J. Respir. Cell Mol. Biol. 32, 504-510
   Abstract »    Full Text »    PDF »
Fasudil prevents KATP channel-induced improvement in postischemic functional recovery.
K. Nishizawa, P. E. Wolkowicz, T. Yamagishi, L.-L. Guo, and M. M. Pike (2005)
Am J Physiol Heart Circ Physiol 288, H3011-H3015
   Abstract »    Full Text »    PDF »
Integrins control motile strategy through a Rho-cofilin pathway.
E. H.J. Danen, J. van Rheenen, W. Franken, S. Huveneers, P. Sonneveld, K. Jalink, and A. Sonnenberg (2005)
J. Cell Biol. 169, 515-526
   Abstract »    Full Text »    PDF »
Antimetastatic Effect of Salvicine on Human Breast Cancer MDA-MB-435 Orthotopic Xenograft Is Closely Related to Rho-Dependent Pathway.
J.-Y. Lang, H. Chen, J. Zhou, Y.-X. Zhang, X.-W. Zhang, M.-H. Li, L.-P. Lin, J.-S. Zhang, M. P. Waalkes, and J. Ding (2005)
Clin. Cancer Res. 11, 3455-3464
   Abstract »    Full Text »    PDF »
{beta}3 Tyrosine Phosphorylation and {alpha}v{beta}3-mediated Adhesion Are Required for Vav1 Association and Rho Activation in Leukocytes.
C. Gao, E. Schaefer, M. Lakkis, and S. D. Blystone (2005)
J. Biol. Chem. 280, 15422-15429
   Abstract »    Full Text »    PDF »
Calcium Signal-induced Cofilin Dephosphorylation Is Mediated by Slingshot via Calcineurin.
Y. Wang, F. Shibasaki, and K. Mizuno (2005)
J. Biol. Chem. 280, 12683-12689
   Abstract »    Full Text »    PDF »
LIM-kinase 2 and Cofilin Phosphorylation Mediate Actin Cytoskeleton Reorganization Induced by Transforming Growth Factor-{beta}.
L. Vardouli, A. Moustakas, and C. Stournaras (2005)
J. Biol. Chem. 280, 11448-11457
   Abstract »    Full Text »    PDF »
ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.
Y. Shimizu, D. Thumkeo, J. Keel, T. Ishizaki, H. Oshima, M. Oshima, Y. Noda, F. Matsumura, M. M. Taketo, and S. Narumiya (2005)
J. Cell Biol. 168, 941-953
   Abstract »    Full Text »    PDF »
{beta}-Arrestin 1 and G{alpha}q/11 Coordinately Activate RhoA and Stress Fiber Formation following Receptor Stimulation.
W. G. Barnes, E. Reiter, J. D. Violin, X.-R. Ren, G. Milligan, and R. J. Lefkowitz (2005)
J. Biol. Chem. 280, 8041-8050
   Abstract »    Full Text »    PDF »
Oncogenic K-RAS Is Required to Maintain Changes in Cytoskeletal Organization, Adhesion, and Motility in Colon Cancer Cells.
C. B. Pollock, S. Shirasawa, T. Sasazuki, W. Kolch, and A. S. Dhillon (2005)
Cancer Res. 65, 1244-1250
   Abstract »    Full Text »    PDF »
A Truncated Tropo-Myosine-Related Kinase B Receptor, T1, Regulates Glial Cell Morphology via Rho GDP Dissociation Inhibitor 1.
K. Ohira, H. Kumanogoh, Y. Sahara, K. J. Homma, H. Hirai, S. Nakamura, and M. Hayashi (2005)
J. Neurosci. 25, 1343-1353
   Abstract »    Full Text »    PDF »
Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization.
C. Radel and V. Rizzo (2005)
Am J Physiol Heart Circ Physiol 288, H936-H945
   Abstract »    Full Text »    PDF »
The role of the Rho GTPases in neuronal development.
E.-E. Govek, S. E. Newey, and L. Van Aelst (2005)
Genes & Dev. 19, 1-49
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Regulation of Retinal Growth Cone Filopodial Dynamics Is Mediated through Actin Depolymerizing Factor/Cofilin.
S. Gehler, A. E. Shaw, P. D. Sarmiere, J. R. Bamburg, and P. C. Letourneau (2004)
J. Neurosci. 24, 10741-10749
   Abstract »    Full Text »    PDF »
The Actin Cytoskeleton Controls the Efficiency of Killer Ig-Like Receptor Accumulation at Inhibitory NK Cell Immune Synapses.
L. J. Standeven, L. M. Carlin, P. Borszcz, D. M. Davis, and D. N. Burshtyn (2004)
J. Immunol. 173, 5617-5625
   Abstract »    Full Text »    PDF »


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