G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants.
G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants.
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DOI：
10.1042/bcj20160819
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发表时间：
2018-11-09
期刊：
影响因子：
--
通讯作者：
Assmann SM
中科院分区：
文献类型：
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作者：
Chakravorty D;Assmann SM
由Gα、Gβ和Gγ亚基组成的异源三聚体G蛋白是真核生物中重要的信号元件，其将配体调节的G蛋白偶联受体（GPCR）的信息传递到细胞效应物。基于异源三聚体G蛋白的信号传导途径是人类健康的基础[Biochimica et Bioproteica Acta（2007）1768，994-1005]，并且是临床使用中>30%的药物的靶标[Biotechnology Advances（2013）31，1676-1694; Nature Reviews Drug Discovery（2017）16，829-842]。本文综述了G蛋白亚基磷酸化在哺乳动物、芽殖酵母和植物中的调节机制。这是一个重新出现的领域，在20世纪90年代初的生物化学研究哺乳动物G蛋白亚基的磷酸化调节的证据，现在可以补充与当代磷酸化蛋白质组学和遗传方法应用于多种模型系统。此外，新的证据表明，植物激酶家族，受体样激酶，这是单系的白细胞介素-1受体相关激酶/Pelle激酶的后生动物，作为可能的GPCR信号通过亚基磷酸化。我们描述了早期和现代的观察G蛋白亚基磷酸化及其在这三类生物的功能后果，并提出了未来的研究方向。
Heterotrimeric G proteins composed of Gα, Gβ, and Gγ subunits are vital eukaryotic signaling elements that convey information from ligand-regulated G protein-coupled receptors (GPCRs) to cellular effectors. Heterotrimeric G protein-based signaling pathways are fundamental to human health [Biochimica et Biophysica Acta (2007) 1768, 994–1005] and are the target of >30% of pharmaceuticals in clinical use [Biotechnology Advances (2013) 31, 1676–1694; Nature Reviews Drug Discovery (2017) 16, 829–842]. This review focuses on phosphorylation of G protein subunits as a regulatory mechanism in mammals, budding yeast, and plants. This is a re-emerging field, as evidence for phosphoregulation of mammalian G protein subunits from biochemical studies in the early 1990s can now be complemented with contemporary phosphoproteomics and genetic approaches applied to a diversity of model systems. In addition, new evidence implicates a family of plant kinases, the receptor-like kinases, which are monophyletic with the interleukin-1 receptor-associated kinase/Pelle kinases of metazoans, as possible GPCRs that signal via subunit phosphorylation. We describe early and modern observations on G protein subunit phosphorylation and its functional consequences in these three classes of organisms, and suggest future research directions.