QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 23, 2005
doi: 10.1242/10.1242/jcs.02675

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pare, G. C. Articles by Kapiloff, M. S. Search for Related Content PubMed PubMed Citation Articles by Pare, G. C. Articles by Kapiloff, M. S. Social Bookmarking                         What's this?

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

Genevieve C. Pare^1,*, Andrea L. Bauman^1,*, Molly McHenry¹, Jennifer J. Carlisle Michel¹, Kimberly L. Dodge-Kafka² and Michael S. Kapiloff^1,

¹ Department of Pediatrics, Department of Cell and Developmental Biology, Heart Research Center, Oregon Health and Science University, NRC5 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA
² Calhoun Center for Cardiology University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA

Author for correspondence (e-mail: kapiloff{at}ohsu.edu)

Accepted 5 September 2005

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 Aß 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.

Key words: mAKAP, Ryanodine receptor, Calcineurin, Hypertrophy, NFATc

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. R. H. Mauban, M. O'Donnell, S. Warrier, S. Manni, and M. Bond AKAP-Scaffolding Proteins and Regulation of Cardiac Physiology Physiology, April 1, 2009; 24(2): 78 - 87. [Abstract] [Full Text] [PDF]

				W. Wong, A. S. Goehring, M. S. Kapiloff, L. K. Langeberg, and J. D. Scott mAKAP Compartmentalizes Oxygen-Dependent Control of HIF-1{alpha} Sci. Signal., December 23, 2008; 1(51): ra18 - ra18. [Abstract] [Full Text] [PDF]

				C. Faul, A. Dhume, A. D. Schecter, and P. Mundel Protein Kinase A, Ca2+/Calmodulin-Dependent Kinase II, and Calcineurin Regulate the Intracellular Trafficking of Myopodin between the Z-Disc and the Nucleus of Cardiac Myocytes Mol. Cell. Biol., December 1, 2007; 27(23): 8215 - 8227. [Abstract] [Full Text] [PDF]