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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.
Pubmed: (View Article at PubMed) PMID:21550986
DOI: Full-text: DOI:10.1074/jbc.M111.231993

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.

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CRRD Object Information
CRRD ID: 6902940
Created: 2012-09-25
Species: All species
Last Modified: 2012-09-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.