Protein kinase D regulates cofilin activity through p21-activated kinase 4.
J Biol Chem
; 286(39): 34254-61, 2011 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-21832093
ABSTRACT
Dynamic reorganization of the actin cytoskeleton at the leading edge is required for directed cell migration. Cofilin, a small actin-binding protein with F-actin severing activities, is a key enzyme initiating such actin remodeling processes. Cofilin activity is tightly regulated by phosphorylation and dephosphorylation events that are mediated by LIM kinase (LIMK) and the phosphatase slingshot (SSH), respectively. Protein kinase D (PKD) is a serine/threonine kinase that inhibits actin-driven directed cell migration by phosphorylation and inactivation of SSH. Here, we show that PKD can also regulate LIMK through direct phosphorylation and activation of its upstream kinase p21-activated kinase 4 (PAK4). Therefore, active PKD increases the net amount of phosphorylated inactive cofilin in cells through both pathways. The regulation of cofilin activity at multiple levels may explain the inhibitory effects of PKD on barbed end formation as well as on directed cell migration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Movimento Celular
/
Actinas
/
Fatores de Despolimerização de Actina
/
Quinases Ativadas por p21
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos