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

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P206516902942PMID:19883655IntAct 
protein binding enablesIPIUniProtKB:P484536902942PMID:19883655IntAct 
protein binding enablesIPIUniProtKB:Q9WVC76902942PMID:19883655IntAct 

Objects Annotated

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


Additional Information