Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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.
Pubmed: (View Article at PubMed) PMID:16306226
DOI: Full-text: DOI:10.1242/jcs.02675

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.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 2312613
Created: 2009-08-25
Species: All species
Last Modified: 2009-08-25
Status: ACTIVE



NHLBI Logo

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