Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure.
Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure.
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DOI：
10.1016/j.ddmec.2010.07.007
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Koch, Walter J
中科院分区：
文献类型：
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作者：
Brinks, Henriette;Koch, Walter J
在人体内，超过1000种不同的G蛋白偶联受体（GPCR）在质膜上介导广谱的细胞外信号，传递重要的生理特征，如疼痛，视觉，嗅觉，炎症，心率和肌肉细胞的收缩性。通过这些受体的信号传导主要由一组激酶GPCR激酶（GRKs）控制和调节，其中只有七种是已知的，因此，干扰这些常见的下游GPCR调节剂表明了一种强大的治疗策略。在心脏中普遍表达的激酶的分子调节已经证明GRK2以及GRK5是预防和逆转人类最严重的病理之一慢性心力衰竭（HF）的有希望的靶标。在这篇文章中，我们将集中在这些GRKs的结构方面，重要的生理和病理调节，以及众所周知的和新的治疗方法，这些GRKs的目标，以克服心脏损伤的发展和HF的进展。
In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF.