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Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase
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.
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Citations
Cited by
Rho GTPases and their effector proteins
BISHOP, A. L., & HALL, A. (2000) · Biochemical Journal · doi:10.1042/bj3480241 · Cited by 2,575
ROCKs: multifunctional kinases in cell behaviour
Riento, K., & Ridley, A. J. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1128 · Cited by 1,941
Burridge, K., & Wennerberg, K. (2004) · Cell · doi:10.1016/s0092-8674(04)00003-0 · Cited by 1,578
Cell migration: Rho GTPases lead the way
Raftopoulou, M., & Hall, A. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2003.06.003 · Cited by 1,235
The ageing cortical synapse: hallmarks and implications for cognitive decline
Morrison, J. H., & Baxter, M. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3200 · Cited by 965
Metadata
- Authors
- Maekawa, M., Ishizaki, T., Boku, S., Watanabe, N., Fujita, A., Iwamatsu, A., Obinata, T., Ohashi, K., Mizuno, K., & Narumiya, S.
- Venue
- Science
- Published
- 1999-08-06
- Volume
- 285
- Issue
- 5429
- Pages
- 895-898
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1995757732
- Cited by
- 1,636
- References
- 0
- FWCI
- 19.46
- Type
- journal article
- Language
- en
- Open access
- closed
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- Maekawa, M., Ishizaki, T., Boku, S., Watanabe, N., Fujita, A., Iwamatsu, A., Obinata, T., Ohashi, K., Mizuno, K., & Narumiya, S. (1999). Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase. Science. https://doi.org/10.1126/science.285.5429.895
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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