RGD Reference Report - An adenylyl cyclase-mAKAPbeta signaling complex regulates cAMP levels in cardiac myocytes. - Rat Genome Database

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An adenylyl cyclase-mAKAPbeta signaling complex regulates cAMP levels in cardiac myocytes.

Authors: Kapiloff, MS  Piggott, LA  Sadana, R  Li, J  Heredia, LA  Henson, E  Efendiev, R  Dessauer, CW 
Citation: Kapiloff MS, etal., J Biol Chem. 2009 Aug 28;284(35):23540-6. Epub 2009 Jul 1.
RGD ID: 6902943
Pubmed: PMID:19574217   (View Abstract at PubMed)
PMCID: PMC2749128   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.030072   (Journal Full-text)

Protein kinase A-anchoring proteins (AKAPs) play important roles in the compartmentation of cAMP signaling, anchoring protein kinase A (PKA) to specific cellular organelles and serving as scaffolds that assemble localized signaling cascades. Although AKAPs have been recently shown to bind adenylyl cyclase (AC), the functional significance of this association has not been studied. In cardiac myocytes, the muscle protein kinase A-anchoring protein beta (mAKAPbeta) coordinates cAMP-dependent, calcium, and MAP kinase pathways and is important for cellular hypertrophy. We now show that mAKAPbeta selectively binds type 5 AC in the heart and that mAKAPbeta-associated AC activity is absent in AC5 knock-out hearts. Consistent with its known inhibition by PKA phosphorylation, AC5 is inhibited by association with mAKAPbeta-PKA complexes. AC5 binds to a unique N-terminal site on mAKAP-(245-340), and expression of this peptide disrupts endogenous mAKAPbeta-AC association. Accordingly, disruption of mAKAPbeta-AC5 complexes in neonatal cardiac myocytes results in increased cAMP and hypertrophy in the absence of agonist stimulation. Taken together, these results show that the association of AC5 with the mAKAPbeta complex is required for the regulation of cAMP second messenger controlling cardiac myocyte hypertrophy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of adenylate cyclase activity  IMP 6902943 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
adenylate cyclase binding enablesIDA 6902943PMID:19574217BHF-UCL 

Objects Annotated

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

Additional Information