RGD Reference Report - The mAKAPbeta scaffold regulates cardiac myocyte hypertrophy via recruitment of activated calcineurin. - Rat Genome Database

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The mAKAPbeta scaffold regulates cardiac myocyte hypertrophy via recruitment of activated calcineurin.

Authors: Li, J  Negro, A  Lopez, J  Bauman, AL  Henson, E  Dodge-Kafka, K  Kapiloff, MS 
Citation: Li J, etal., J Mol Cell Cardiol. 2010 Feb;48(2):387-94. Epub 2009 Oct 31.
RGD ID: 6902942
Pubmed: PMID:19883655   (View Abstract at PubMed)
PMCID: PMC2813376   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yjmcc.2009.10.023   (Journal Full-text)

mAKAPbeta is the scaffold for a multimolecular signaling complex in cardiac myocytes that is required for the induction of neonatal myocyte hypertrophy. We now show that the pro-hypertrophic phosphatase calcineurin binds directly to a single site on mAKAPbeta that does not conform to any of the previously reported consensus binding sites. Calcineurin-mAKAPbeta complex formation is increased in the presence of Ca(2+)/calmodulin and in norepinephrine-stimulated primary cardiac myocytes. This binding is of functional significance because myocytes exhibit diminished norepinephrine-stimulated hypertrophy when expressing a mAKAPbeta mutant incapable of binding calcineurin. In addition to calcineurin, the transcription factor NFATc3 also associates with the mAKAPbeta scaffold in myocytes. Calcineurin bound to mAKAPbeta can dephosphorylate NFATc3 in myocytes, and expression of mAKAPbeta is required for NFAT transcriptional activity. Taken together, our results reveal the importance of regulated calcineurin binding to mAKAPbeta for the induction of cardiac myocyte hypertrophy. Furthermore, these data illustrate how scaffold proteins organizing localized signaling complexes provide the molecular architecture for signal transduction networks regulating key cellular processes.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Akap6Ratprotein binding enablesIPIUniProtKB:P20651PMID:19883655IntAct 
Akap6Ratprotein binding enablesIPIUniProtKB:P48453PMID:19883655IntAct 
Ppp3cbRatprotein binding enablesIPIUniProtKB:Q9WVC7PMID:19883655IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Akap6  (A-kinase anchoring protein 6)
Ppp3cb  (protein phosphatase 3 catalytic subunit beta)


Additional Information