Essential role of β-adrenergic receptor kinase 1 in cardiac development and function
In: Proceedings of the National Academy of Sciences, Jg. 93 (1996-11-12), S. 12974-12979
Online
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Zugriff:
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 direct in 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.
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Essential role of β-adrenergic receptor kinase 1 in cardiac development and function
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Autor/in / Beteiligte Person: | Smith, Bradley R. ; Koch, Walter J. ; Caron, Marc G. ; Sulik, Kathleen K. ; Bond, Richard A. ; Giros, Bruno ; Ross, John ; Lefkowitz, Robert J. ; Jaber, Mohamed ; Rockman, Howard A. |
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Zeitschrift: | Proceedings of the National Academy of Sciences, Jg. 93 (1996-11-12), S. 12974-12979 |
Veröffentlichung: | Proceedings of the National Academy of Sciences, 1996 |
Medientyp: | unknown |
ISSN: | 1091-6490 (print) ; 0027-8424 (print) |
DOI: | 10.1073/pnas.93.23.12974 |
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