A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase

FEBS Lett. 2010 Feb 5;584(3):631-7. doi: 10.1016/j.febslet.2009.12.014. Epub 2009 Dec 14.


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.

MeSH terms

  • Animals
  • Histone Deacetylases / metabolism*
  • Immunoblotting
  • Immunoprecipitation
  • Myocardium / enzymology*
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley


  • Protein Kinase Inhibitors
  • protein kinase D
  • Protein Kinase C
  • Histone Deacetylases