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

Publication ,  Journal Article
Keys, JR; Greene, EA; Cooper, CJ; Naga Prasad, SV; Rockman, HA; Koch, WJ
Published in: Am J Physiol Heart Circ Physiol
November 2003

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.

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Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

November 2003

Volume

285

Issue

5

Start / End Page

H2201 / H2211

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • RGS Proteins
  • Protein Structure, Tertiary
  • Mice, Transgenic
  • Mice
  • Heart
  • Gene Expression Regulation, Enzymologic
  • Down-Regulation
 

Citation

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Keys, J. R., Greene, E. A., Cooper, C. J., Naga Prasad, S. V., Rockman, H. A., & Koch, W. J. (2003). Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1. Am J Physiol Heart Circ Physiol, 285(5), H2201–H2211. https://doi.org/10.1152/ajpheart.00112.2003
Keys, Janelle R., Emily A. Greene, Chris J. Cooper, Sathyamangla V. Naga Prasad, Howard A. Rockman, and Walter J. Koch. “Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1.Am J Physiol Heart Circ Physiol 285, no. 5 (November 2003): H2201–11. https://doi.org/10.1152/ajpheart.00112.2003.
Keys JR, Greene EA, Cooper CJ, Naga Prasad SV, Rockman HA, Koch WJ. Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1. Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H2201–11.
Keys, Janelle R., et al. “Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1.Am J Physiol Heart Circ Physiol, vol. 285, no. 5, Nov. 2003, pp. H2201–11. Pubmed, doi:10.1152/ajpheart.00112.2003.
Keys JR, Greene EA, Cooper CJ, Naga Prasad SV, Rockman HA, Koch WJ. Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1. Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H2201–H2211.

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

November 2003

Volume

285

Issue

5

Start / End Page

H2201 / H2211

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • RGS Proteins
  • Protein Structure, Tertiary
  • Mice, Transgenic
  • Mice
  • Heart
  • Gene Expression Regulation, Enzymologic
  • Down-Regulation