A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase.
FEBS Lett
; 584(3): 631-7, 2010 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-20018189
ABSTRACT
Class IIa histone deacetylases (HDACs) repress genes involved in pathological cardiac hypertrophy. The anti-hypertrophic action of class IIa HDACs is overcome by signals that promote their phosphorylation-dependent nuclear export. Several kinases have been shown to phosphorylate class IIa HDACs, including calcium/calmodulin-dependent protein kinase (CaMK), protein kinase D (PKD) and G protein-coupled receptor kinase (GRK). However, the identity of the kinase(s) responsible for phosphorylating class IIa HDACs during cardiac hypertrophy has remained controversial. We describe a novel and selective small molecule inhibitor of PKD, bipyridyl PKD inhibitor (BPKDi). BPKDi blocks signal-dependent phosphorylation and nuclear export of class IIa HDACs in cardiomyocytes and concomitantly suppresses hypertrophy of these cells. These studies define PKD as a principal cardiac class IIa HDAC kinase.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Inibidores de Proteínas Quinases
/
Histona Desacetilases
/
Miocárdio
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos