Biology Department, Penn State University, 208 Mueller Laboratory, University Park, PA 16802, U.S.A.
Biochem J. 2018 Nov 9;475(21):3331-3357. doi: 10.1042/BCJ20160819.
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 [ (2007) , 994-1005] and are the target of >30% of pharmaceuticals in clinical use [ (2013) , 1676-1694; (2017) , 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.
异三聚体 G 蛋白由 Gα、Gβ 和 Gγ 亚基组成，是从配体调节的 G 蛋白偶联受体 (GPCR) 向细胞效应器传递信息的重要真核信号元件。基于异三聚体 G 蛋白的信号通路是人类健康的基础[ (2007), 994-1005]，也是临床使用的 >30%药物的靶点[ (2013), 1676-1694; (2017), 829-842]。这篇综述重点介绍了磷酸化作为哺乳动物、芽殖酵母和植物中 G 蛋白亚基的调节机制。这是一个重新出现的领域，因为 20 世纪 90 年代早期生化研究中关于哺乳动物 G 蛋白亚基磷酸化的证据，现在可以通过当代磷酸蛋白质组学和遗传方法应用于多种模型系统来补充。此外，新的证据表明，一类植物激酶，即受体样激酶，与后生动物的白细胞介素-1 受体相关激酶/ Pelle 激酶具有单系性，可能是通过亚基磷酸化信号转导的 GPCR。我们描述了这三类生物体中 G 蛋白亚基磷酸化及其功能后果的早期和现代观察结果，并提出了未来的研究方向。
