PMID- 16767219
OWN - NLM
STAT- MEDLINE
DCOM- 20060926
LR  - 20220819
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 7
DP  - 2006 Jul
TI  - CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte 
      hypertrophy.
PG  - 1853-64
AB  - Class IIa histone deacetylases (HDACs) regulate a variety of cellular processes, 
      including cardiac growth, bone development, and specification of skeletal muscle 
      fiber type. Multiple serine/threonine kinases control the subcellular 
      localization of these HDACs by phosphorylation of common serine residues, but 
      whether certain class IIa HDACs respond selectively to specific kinases has not 
      been determined. Here we show that calcium/calmodulin-dependent kinase II 
      (CaMKII) signals specifically to HDAC4 by binding to a unique docking site that 
      is absent in other class IIa HDACs. Phosphorylation of HDAC4 by CaMKII promotes 
      nuclear export and prevents nuclear import of HDAC4, with consequent derepression 
      of HDAC target genes. In cardiomyocytes, CaMKII phosphorylation of HDAC4 results 
      in hypertrophic growth, which can be blocked by a signal-resistant HDAC4 mutant. 
      These findings reveal a central role for HDAC4 in CaMKII signaling pathways and 
      have implications for the control of gene expression by calcium signaling in a 
      variety of cell types.
FAU - Backs, Johannes
AU  - Backs J
AD  - Department of Molecular Biology, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390-9148, USA.
FAU - Song, Kunhua
AU  - Song K
FAU - Bezprozvannaya, Svetlana
AU  - Bezprozvannaya S
FAU - Chang, Shurong
AU  - Chang S
FAU - Olson, Eric N
AU  - Olson EN
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060608
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.5.1.98 (HDAC4 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - 14-3-3 Proteins/metabolism
MH  - Active Transport, Cell Nucleus/physiology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism
MH  - Cell Nucleus/metabolism
MH  - Chlorocebus aethiops
MH  - Enzyme Activation
MH  - Histone Deacetylases/genetics/*metabolism
MH  - Hypertrophy
MH  - Isoenzymes/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - *Myocytes, Cardiac/cytology/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Sequence Alignment
MH  - Signal Transduction/*physiology
MH  - Two-Hybrid System Techniques
PMC - PMC1474817
EDAT- 2006/06/13 09:00
MHDA- 2006/09/27 09:00
PMCR- 2006/07/03
CRDT- 2006/06/13 09:00
PHST- 2005/11/17 00:00 [received]
PHST- 2006/04/18 00:00 [accepted]
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2006/09/27 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
PHST- 2006/07/03 00:00 [pmc-release]
AID - 27438 [pii]
AID - 10.1172/JCI27438 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 Jul;116(7):1853-64. doi: 10.1172/JCI27438. Epub 2006 Jun 8.