Nuclear effects of G-protein receptor kinase 5 on histone deacetylase 5-regulated gene transcription in heart failure.

ABSTRACT:

Background

G-protein receptor kinases (GRKs) modulate cardiac β-adrenergic signaling. GRK5 is upregulated in heart failure, and a gain-of-function polymorphism substituting leucine for wild-type glutamine at amino acid 41 (GRK5-Leu41) is associated with improved outcomes in heart failure and hypertension. GRK5 is distinguished by partial nuclear localization and class II histone deacetylases (HDAC) kinase activity that is postulated to regulate Gαq-stimulated cardiac gene expression.

Methods and results

We used in vitro tissue culture and in vivo mouse compound genetic models to examine the effects of GRK5 on HDAC phosphorylation, nucleo-cytoplasmic HDAC transport, and Gαq-dependent transcriptional regulation. In vitro, GRK5 stimulated HDAC5 nuclear export only in the contex

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3178677 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature