Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.
Science
; 285(5429): 895-8, 1999 Aug 06.
Article
em En
| MEDLINE
| ID: mdl-10436159
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Citoesqueleto de Actina
/
Transdução de Sinais
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ligação ao GTP
/
GTP Fosfo-Hidrolases
/
Proteínas de Membrana
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Japão