Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1.
Nat Cell Biol
; 4(9): 681-90, 2002 Sep.
Article
en En
| MEDLINE
| ID: mdl-12198493
ABSTRACT
The serine/threonine kinase p21-activated kinase 1 (Pak1) controls the actin cytoskeletal and ruffle formation through mechanisms that are independent of GTPase activity. Here we identify filamin FLNa as a Pak1-interacting protein through a yeast two-hybrid screen using the amino terminus of Pak1 as a bait. FLNa is stimulated by physiological signalling molecules to undergo phosphorylation by Pak1 and to interact and colocalize with endogenous Pak1 in membrane ruffles. The ruffle-forming activity of Pak1 is functional in FLNa-expressing cells but not in FLNa-deficient cells. In FLNa, the Pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152. The FLNa-binding site in Pak1 is localized between amino acids 52 and 132 in the conserved Cdc42/Rac-interacting (CRIB) domain; accordingly, FLNa binding to the CRIB domain stimulates Pak1 kinase activity. Our results indicate that FLNa may be essential for Pak1-induced cytoskeletal reorganization and that the two-way regulatory interaction between Pak1 and FLNa may contribute to the local stimulation of Pak1 activity and its targets in cytoskeletal structures.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Actinas
/
Proteínas Serina-Treonina Quinasas
/
Proteínas Contráctiles
/
Proteínas de Microfilamentos
Límite:
Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos