Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1.

Journal Article (Journal Article)

The G protein-coupled receptor (GPCR) kinase beta-adrenergic receptor (beta-AR) kinase-1 (beta-ARK1) is elevated during heart failure; however, its role is not fully understood. Beta-ARK1 contains several domains that are 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 that is comprised of amino acid residues 50-145 (beta-ARKnt) in the heart to determine whether 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 to be critical for normal beta-AR regulation in vivo, which further supports the hypothesis that beta-ARK1 plays a key role in normal and compromised cardiac GPCR signaling.

Full Text

Duke Authors

Cited Authors

  • Keys, JR; Greene, EA; Cooper, CJ; Naga Prasad, SV; Rockman, HA; Koch, WJ

Published Date

  • November 2003

Published In

Volume / Issue

  • 285 / 5

Start / End Page

  • H2201 - H2211

PubMed ID

  • 12869383

International Standard Serial Number (ISSN)

  • 0363-6135

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.00112.2003


  • eng

Conference Location

  • United States