RGD Reference Report - The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling. - Rat Genome Database

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The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling.

Authors: Pare, GC  Bauman, AL  McHenry, M  Michel, JJ  Dodge-Kafka, KL  Kapiloff, MS 
Citation: Pare GC, etal., J Cell Sci. 2005 Dec 1;118(Pt 23):5637-46.
RGD ID: 2312613
Pubmed: PMID:16306226   (View Abstract at PubMed)
DOI: DOI:10.1242/jcs.02675   (Journal Full-text)

Maladaptive cardiac hypertrophy can progress to congestive heart failure, a leading cause of morbidity and mortality in the United States. A better understanding of the intracellular signal transduction network that controls myocyte cell growth may suggest new therapeutic directions. mAKAP is a scaffold protein that has recently been shown to coordinate signal transduction enzymes important for cytokine-induced cardiac hypertrophy. We now extend this observation and show mAKAP is important for adrenergic-mediated hypertrophy. One function of the mAKAP complex is to facilitate cAMP-dependent protein kinase A-catalyzed phosphorylation of the ryanodine receptor Ca2+-release channel. Experiments utilizing inhibition of the ryanodine receptor, RNA interference of mAKAP expression and replacement of endogenous mAKAP with a mutant form that does not bind to protein kinase A demonstrate that the mAKAP complex contributes to pro-hypertrophic signaling. Further, we show that calcineurin Abeta associates with mAKAP and that the formation of the mAKAP complex is required for the full activation of the pro-hypertrophic transcription factor NFATc. These data reveal a novel function of the mAKAP complex involving the integration of cAMP and Ca2+ signals that promote myocyte hypertrophy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein-containing complex  IDA 2312613; 2312613; 2312613 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein domain specific binding  IDA 2312613Akap6RGD 
protein kinase A regulatory subunit binding  IDA 2312613Prkar2aRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akap6  (A-kinase anchoring protein 6)
Ppp3cb  (protein phosphatase 3 catalytic subunit beta)
Prkar2a  (protein kinase cAMP-dependent type II regulatory subunit alpha)
Ryr2  (ryanodine receptor 2)


Additional Information