| First Author | Keys JR | Year | 2003 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 285 |
| Issue | 5 | Pages | H2201-11 |
| PubMed ID | 12869383 | Mgi Jnum | J:128782 |
| Mgi Id | MGI:3768014 | Doi | 10.1152/ajpheart.00112.2003 |
| Citation | Keys JR, et al. (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):H2201-11 |
| abstractText | 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. |
