Ubiquitin-dependent regulation of G protein-coupled receptor trafficking and signaling.
Ubiquitin-dependent regulation of G protein-coupled receptor trafficking and signaling.
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DOI：
10.1016/j.cellsig.2012.11.024
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发表时间：
2013-03
影响因子：
4.8
通讯作者：
Trejo J
中科院分区：
文献类型：
--
作者：
Marchese A;Trejo J
G蛋白偶联受体(GPCRs)是哺乳动物基因组中最大的信号受体家族之一。GPCRs激发细胞对多种不同刺激的反应，在人类健康和疾病中发挥重要作用。GPCRs在各种疾病中具有重要的临床意义，大约25%-50%的上市药物是GPCRs的靶标。了解GPCRs是如何调控的，对于描述它们在正常生理学和几种疾病的病理生理学中的作用是至关重要的。鉴于GPCRs的数量和多样性，很可能存在多种机制来调节GPCRs的功能。虽然gpr信号通常是由磷酸化和β抑制蛋白介导的脱敏和内吞作用调节的，但它也可以受到泛素化的调节。泛素化正在成为一个重要的调控过程，它可能在管理GPCR的贩运和信号传递方面发挥独特的作用。最近的研究揭示了GPCR磷酸化、β抑制蛋白和泛素化之间的机制联系，这种联系可能适用于某些GPCRs，但不适用于其他GPCRs。虽然泛素化的功能通常被认为促进受体内吞和内体分选，但最近的研究表明，泛素化在GPCR信号的正向调节中也发挥着重要作用。在这里，我们将回顾我们的最新进展，我们的理解泛素如何调节GPCR胞内运输，以及它如何在GPCR活化诱导的信号转导中发挥作用。
G protein-coupled receptors (GPCRs) belong to one of the largest family of signaling receptors in the mammalian genome. GPCRs elicit cellular responses to multiple diverse stimuli and play essential roles in human health and disease. GPCRs have important clinical implications in various diseases and are the targets of approximately 25–50% of all marketed drugs. Understanding how GPCRs are regulated is essential to delineating their role in normal physiology and in the pathophysiology of several diseases. Given the vast number and diversity of GPCRs, it is likely that multiple mechanisms exist to regulate GPCR function. While GPCR signaling is typically regulated by desensitization and endocytosis mediated by phosphorylation and β-arrestins, it can also be modulated by ubiquitination. Ubiquitination is emerging an important regulatory process that may have unique roles in governing GPCR trafficking and signaling. Recent studies have revealed a mechanistic link between GPCR phosphorylation, β-arrestins and ubiquitination that may be applicable to some GPCRs but not others. While the function of ubiquitination is generally thought to promote receptor endocytosis and endosomal sorting, recent studies have revealed that ubiquitination also plays an important role in positive regulation of GPCR signaling. Here, we will review recent developments in our understanding of how ubiquitin regulates GPCR endocytic trafficking and how it contributes to signal transduction induced by GPCR activation.
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影响因子：
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