Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function
Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function
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DOI：
10.1073/pnas.93.23.12974
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Giros, B
中科院分区：
文献类型：
--
作者：
Jaber, M;Koch, WJ;Giros, B
β-肾上腺素能受体激酶1（beta-adrenergic receptor kinase 1，beta ARK 1）是G蛋白偶联受体激酶（G protein-coupled receptor kinase，GRK）家族的一员，它介导激动剂依赖性的磷酸化和G蛋白偶联受体的脱敏。在妊娠第15.5天之前，β ARK 1（-/-）胚胎显示出明显的心室肌发育不全，基本上与在几种转录因子（RXR α、N-myc、TEF-1、WT-1）基因失活后观察到的“薄心肌综合征”相同。β ARK 1（-/-）胚胎的致死性可能是由于心力衰竭，因为通过子宫内活体显微镜直接测定，它们表现出心脏射血分数降低>70%。这些结果沿着在β ARK 1（-/-）胚胎中内源性GRK活性的实际缺乏，表明β ARK 1似乎是早期胚胎发生中的主要GRK，并且它在心脏发育中起着基本作用。
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.