Open AccessEssential role of β-adrenergic receptor kinase 1 in cardiac development and function
Author(s) -
Mohamed Jaber,
Walter J. Koch,
Howard A. Rockman,
Brian N. Smith,
Richard A. Bond,
Kathleen K. Sulik,
John Ross,
Robert J. Lefkowitz,
Marc G. Caron,
Bruno Giros
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.23.12974
Subject(s) - beta adrenergic receptor kinase , biology , endocrinology , microbiology and biotechnology , embryo , medicine , receptor , kinase , agonist , protein kinase a , adrenergic receptor , cardiac function curve , signal transduction , heart failure , g protein coupled receptor , genetics
The β-adrenergic receptor kinase 1 (βARK1) 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 βARK1 gene in mice by homologous recombination. No homozygote βARK1−/− embryos survive beyond gestational day 15.5. Prior to gestational day 15.5, βARK1−/− embryos display pronounced hypoplasia of the ventricular myocardium essentially identical to the “thin myocardium syndrome” observed upon gene inactivation of several transcription factors (RXRα, N-myc , TEF-1, WT-1). Lethality in βARK1−/− embryos is likely due to heart failure as they exhibit a >70% decrease in cardiac ejection fraction determined by directin utero intravital microscopy. These results along with the virtual absence of endogenous GRK activity in βARK1−/− embryos demonstrate that βARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development.