Publication Date:
1999-08-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maekawa, M -- Ishizaki, T -- Boku, S -- Watanabe, N -- Fujita, A -- Iwamatsu, A -- Obinata, T -- Ohashi, K -- Mizuno, K -- Narumiya, S -- New York, N.Y. -- Science. 1999 Aug 6;285(5429):895-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8315, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10436159" target="_blank"〉PubMed〈/a〉
Keywords:
Actin Cytoskeleton/*metabolism
;
Actin Depolymerizing Factors
;
Actins/metabolism
;
Amides/pharmacology
;
Animals
;
COS Cells
;
DNA-Binding Proteins/metabolism
;
Enzyme Activation
;
GTP Phosphohydrolases/*metabolism
;
GTP-Binding Proteins/*metabolism
;
HeLa Cells
;
Humans
;
Intracellular Signaling Peptides and Proteins
;
Lim Kinases
;
Lysophospholipids/pharmacology
;
Membrane Proteins/*metabolism
;
Microfilament Proteins/metabolism
;
Phosphorylation
;
Protein Kinases/*metabolism
;
Protein-Serine-Threonine Kinases/*metabolism
;
Pyridines/pharmacology
;
*Signal Transduction
;
Tumor Cells, Cultured
;
rho-Associated Kinases
;
rhoB GTP-Binding Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
