Cardiac hypertrophy and altered {beta}-adrenergic signaling in transgenic mice expressing the amino terminus of {beta}ARK1

Keys, Janelle R., Greene, Emily A., Cooper, Chris J., Naga Prasad, Sathyamangla V., Rockman, Howard A. and Koch, Walter J. (2003) Cardiac hypertrophy and altered {beta}-adrenergic signaling in transgenic mice expressing the amino terminus of {beta}ARK1. American journal of physiology Heart and circulatory physiology, 285 5: 2201-2211.


Author Keys, Janelle R.
Greene, Emily A.
Cooper, Chris J.
Naga Prasad, Sathyamangla V.
Rockman, Howard A.
Koch, Walter J.
Title Cardiac hypertrophy and altered {beta}-adrenergic signaling in transgenic mice expressing the amino terminus of {beta}ARK1
Formatted title
Cardiac Hypertrophy and Altered ß-adrenergic Signaling in Transgenic Mice Expressing the Amino Terminus of ßARK1
Journal name American journal of physiology Heart and circulatory physiology   Check publisher's open access policy
ISSN 1522-1539
Publication date 2003-11-01
Sub-type Article (original research)
Open Access Status Not Open Access
Volume 285
Issue 5
Start page 2201
End page 2211
Total pages 11
Place of publication Bethesda, MD
Publisher American Physiological Society
Language eng
Subject 1102 Cardiovascular Medicine and Haematology
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Abstract The G protein-coupled receptor (GPCR) kinase, {beta}-adrenergic receptor ({beta}AR) kinase ({beta}ARK1) is elevated in heart failure, however its role is not fully understood. {beta}ARK1 contains several domains capable of protein-protein interactions that may play critical roles in the regulation of GPCR signaling. In this study, we developed a novel line of transgenic mice that express an amino-terminal peptide of {beta}ARK1, comprised of amino acid residues 50-145 ({beta}ARKnt), in the heart, to determine if this domain has any functional significance in vivo. Surprisingly, the {beta}ARKnt transgenic mice presented with cardiac hypertrophy. Our data suggest that the phenotype was driven via an enhanced {beta}AR system, as {beta}ARKnt mice had elevated cardiac {beta}AR density. Moreover, administration of a {beta}AR antagonist reversed hypertrophy in these mice. Interestingly, signaling through the {beta}AR in response to agonist stimulation was not enhanced in these mice. Thus, the amino terminus of {beta}ARK1 appears critical for normal {beta}AR regulation in vivo, and further supports the hypothesis that {beta}ARK1 plays a key role in normal and compromised cardiac GPCR signaling.
Keyword Kinase
Mice
Cardiovascular
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 11 Feb 2009, 22:36:10 EST by Gina Velli on behalf of Institute for Molecular Bioscience