Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function.

Published

Journal Article

The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. We have cloned and disrupted the beta ARK1 gene in mice by homologous recombination. No homozygote beta ARK1-/- embryos survive beyond gestational day 15.5. Prior to gestational day 15.5, beta ARK1-/- embryos display pronounced hypoplasia of the ventricular myocardium essentially identical to the "thin myocardium syndrome" observed upon gene inactivation of several transcription factors (RXR alpha, N-myc, TEF-1, WT-1). Lethality in beta ARK1-/- embryos is likely due to heart failure as they exhibit a > 70% decrease in cardiac ejection fraction determined by direct in utero intravital microscopy. These results along with the virtual absence of endogenous GRK activity in beta ARK1-/- embryos demonstrate that beta ARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development.

Full Text

Duke Authors

Cited Authors

  • Jaber, M; Koch, WJ; Rockman, H; Smith, B; Bond, RA; Sulik, KK; Ross, J; Lefkowitz, RJ; Caron, MG; Giros, B

Published Date

  • November 12, 1996

Published In

Volume / Issue

  • 93 / 23

Start / End Page

  • 12974 - 12979

PubMed ID

  • 8917529

Pubmed Central ID

  • 8917529

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.93.23.12974

Language

  • eng

Conference Location

  • United States