RGD Reference Report - Phospholipase C epsilon scaffolds to muscle-specific A kinase anchoring protein (mAKAPbeta) and integrates multiple hypertrophic stimuli in cardiac myocytes. - Rat Genome Database

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Phospholipase C epsilon scaffolds to muscle-specific A kinase anchoring protein (mAKAPbeta) and integrates multiple hypertrophic stimuli in cardiac myocytes.

Authors: Zhang, L  Malik, S  Kelley, GG  Kapiloff, MS  Smrcka, AV 
Citation: Zhang L, etal., J Biol Chem. 2011 Jul 1;286(26):23012-21. Epub 2011 May 5.
RGD ID: 6902940
Pubmed: PMID:21550986   (View Abstract at PubMed)
PMCID: PMC3123069   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.231993   (Journal Full-text)

To define a role for phospholipase Cepsilon (PLCepsilon) signaling in cardiac myocyte hypertrophic growth, PLCepsilon protein was depleted from neonatal rat ventricular myocytes (NRVMs) using siRNA. NRVMs with PLCepsilon depletion were stimulated with endothelin (ET-1), norepinephrine, insulin-like growth factor-1 (IGF-1), or isoproterenol and assessed for development of hypertrophy. PLCepsilon depletion dramatically reduced hypertrophic growth and gene expression induced by all agonists tested. PLCepsilon catalytic activity was required for hypertrophy development, yet PLCepsilon depletion did not reduce global agonist-stimulated inositol phosphate production, suggesting a requirement for localized PLC activity. PLCepsilon was found to be scaffolded to a muscle-specific A kinase anchoring protein (mAKAPbeta) in heart and NRVMs, and mAKAPbeta localizes to the nuclear envelope in NRVMs. PLCepsilon-mAKAP interaction domains were defined and overexpressed to disrupt endogenous mAKAPbeta-PLCepsilon complexes in NRVMs, resulting in significantly reduced ET-1-dependent NRVM hypertrophy. We propose that PLCepsilon integrates multiple upstream signaling pathways to generate local signals at the nucleus that regulate hypertrophy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell growth involved in cardiac muscle cell development  IMP 6902940 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akap6  (A-kinase anchoring protein 6)


Additional Information