RGD Reference Report - Regulation of cardiac stress signaling by protein kinase d1. - Rat Genome Database

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Regulation of cardiac stress signaling by protein kinase d1.

Authors: Harrison, Brooke C  Kim, Mi-Sung  van Rooij, Eva  Plato, Craig F  Papst, Philip J  Vega, Rick B  McAnally, John A  Richardson, James A  Bassel-Duby, Rhonda  Olson, Eric N  McKinsey, Timothy A 
Citation: Harrison BC, etal., Mol Cell Biol. 2006 May;26(10):3875-88. doi: 10.1128/MCB.26.10.3875-3888.2006.
RGD ID: 243065275
Pubmed: PMID:16648482   (View Abstract at PubMed)
PMCID: PMC1488991   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.26.10.3875-3888.2006   (Journal Full-text)

In response to pathological stresses such as hypertension or myocardial infarction, the heart undergoes a remodeling process that is associated with myocyte hypertrophy, myocyte death, and fibrosis. Histone deacetylase 5 (HDAC5) is a transcriptional repressor of cardiac remodeling that is subject to phosphorylation-dependent neutralization in response to stress signaling. Recent studies have suggested a role for protein kinase C (PKC) and its downstream effector, protein kinase D1 (PKD1), in the control of HDAC5 phosphorylation. While PKCs are well-documented regulators of cardiac signaling, the function of PKD1 in heart muscle remains unclear. Here, we demonstrate that PKD1 catalytic activity is stimulated in cardiac myocytes by diverse hypertrophic agonists that signal through G protein-coupled receptors (GPCRs) and Rho GTPases. PKD1 activation in cardiomyocytes occurs through PKC-dependent and -independent mechanisms. In vivo, cardiac PKD1 is activated in multiple rodent models of pathological cardiac remodeling. PKD1 activation correlates with phosphorylation-dependent nuclear export of HDAC5, and reduction of endogenous PKD1 expression with small interfering RNA suppresses HDAC5 shuttling and associated cardiomyocyte growth. Conversely, ectopic overexpression of constitutively active PKD1 in mouse heart leads to dilated cardiomyopathy. These findings support a role for PKD1 in the control of pathological remodeling of the heart via its ability to phosphorylate and neutralize HDAC5.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PRKD1HumanCardiomegaly  IMP human gene in a mouse modelRGD 
PRKD1HumanCardiomegaly  ISOPrkd1 (Rattus norvegicus)protein:increased phosphorylation:heart left ventricle (rat)RGD 
Prkd1RatCardiomegaly  ISOPRKD1 (Homo sapiens)human gene in a mouse modelRGD 
Prkd1RatCardiomegaly  IEP protein:increased phosphorylation:heart left ventricle (rat)RGD 
Prkd1MouseCardiomegaly  ISOPRKD1 (Homo sapiens)human gene in a mouse modelRGD 
Prkd1MouseCardiomegaly  ISOPrkd1 (Rattus norvegicus)protein:increased phosphorylation:heart left ventricle (rat)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PRKD1Humanlysophosphatidic acid increases phosphorylationISOPrkd1 (Rattus norvegicus)LPA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Ratlysophosphatidic acid increases phosphorylationEXP LPA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Mouselysophosphatidic acid increases phosphorylationISOPrkd1 (Rattus norvegicus)LPA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
PRKD1Humanphenylephrine increases phosphorylationISOPrkd1 (Rattus norvegicus)Phenylephrine increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Ratphenylephrine increases phosphorylationEXP Phenylephrine increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Mousephenylephrine increases phosphorylationISOPrkd1 (Rattus norvegicus)Phenylephrine increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
PRKD1Humanphorbol 13-acetate 12-myristate increases phosphorylationISOPrkd1 (Rattus norvegicus)PMA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Ratphorbol 13-acetate 12-myristate increases phosphorylationEXP PMA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 
Prkd1Mousephorbol 13-acetate 12-myristate increases phosphorylationISOPrkd1 (Rattus norvegicus)PMA increases phosphorylation of Prkd1 protein in neonatal ventricular myocytesRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Prkd1Ratcellular response to endothelin  IDA  RGD 
Prkd1Ratpositive regulation of cell size  IMP CardiomyocytesRGD 
Prkd1Ratpositive regulation of peptide hormone secretion  IMP Atrial natriuretic factorRGD 
Prkd1Ratpositive regulation of protein export from nucleus  IMP Hdac5RGD 
Prkd1Ratpositive regulation of sarcomere organization  IMP  RGD 
Prkd1Ratresponse to norepinephrine  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Prkd1Ratnucleus  IDA  RGD 
Prkd1Ratperinuclear region of cytoplasm  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Prkd1Ratprotein kinase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkd1  (protein kinase D1)

Genes (Mus musculus)
Prkd1  (protein kinase D1)

Genes (Homo sapiens)
PRKD1  (protein kinase D1)


Additional Information