《分子细胞生物学》（Molecular and Cellular Biology）近日发表了中科院上海生命科学研究院营养所营养与代谢重点实验室陈雁研究组博士生蒋玉辉等对于RKTG调控Gβγ功能的最新研究结果。
G蛋白偶联受体（GPCR）参与了机体内多种生理过程的调节，是目前治疗多种人类疾病包括代谢性疾病的药物靶点。GPCR的G蛋白部分由Gα，β，γ三个亚基组成，受体激活后，其信号转导主要由α亚基进行。但近年来的研究表明，Gβγ可以不依赖Gα发挥许多重要的生理功能，如调节离子通道、磷脂酰肌醇激酶以及G蛋白偶联受体激酶（GRK）等重要的细胞内分子。
RKTG是一个特异表达在细胞器高尔基体的一个膜蛋白。研究人员首先发现RKTG与Gβγ相互作用，在空间上把细胞内的Gβγ转移到高尔基体，发现RKTG通过改变Gβγ空间位置对细胞生理功能带来影响。RKTG能够与GRK竞争性结合Gβγ，影响了GRK介导的G蛋白偶联受体内吞，进而影响了G蛋白信号通路的脱敏效应。RKTG 通过与Gβγ结合，影响了Gβγ下游的PI3K/AKT信号通路。RKTG与Gβγ结合时间曲线与AKT活化时间曲线呈负相关，而RKTG的缺失，减少了GPCR激活后Gβγ在高尔基体的分布以及AKT的活化。
该项研究发现了调控Gβγ功能的一个全新机制，对于深入了解G蛋白信号通路有着重要的意义。另外，由于Gβγ下游效应分子参与了多个细胞功能的调节，该研究为未来医学领域中一些疾病的治疗增添了新的理论基础以及药物靶点。
该研究受到科技部重大科学研究计划，国家基金委重点项目、杰出青年基金，中科院重大项目等基金的支持。（生物谷Bioon.com）
生物谷推荐原始出处：
Mol. Cell. Biol. doi:10.1128/MCB.01038-09
Regulation of G protein signaling by RKTG via sequestrating Gbetagamma subunit to Golgi apparatus
Yuhui Jiang, Xiaoduo Xie, Yixuan Zhang, Xiaolin Luo, Xiao Wang, Fengjuan Fan, Dawei Zheng, Zhenzhen Wang, and Yan Chen*
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Upon ligand binding, G protein coupled receptors (GPCRs) impart the signal to heterotrimeric G proteins composed of , and subunits, leading to dissociation of G subunit from G subunit. While the G subunit is imperative for downstream signaling, the G subunit, in its own right, mediates a variety of cellular responses such as GPCR desensitization via recruiting GRK to plasma membrane and AKT stimulation. Here we report a mode of spatial regulation of G subunit through alteration in subcellular compartmentation. RKTG (Raf Kinase Trapping to Golgi) is a newly characterized membrane protein specifically localized at the Golgi apparatus. The N-terminus of RKTG interacts with Gand tethers G to the Golgi. Overexpression of RKTG impedes the interaction of G with GRK2, abrogates the ligand-induced change of subcellular distribution of GRK2, reduces isoproterenol-stimulated phosphorylation of 2-adrenergic receptor (2AR), and alters 2AR desensitization. In addition, RKTG inhibits G- and ligand-mediated AKT that is enhanced in cells with downregulation of RKTG. Silencing of RKTG also enhances GRK2 internalization and compromises ligand-induced G translocation to the Golgi apparatus. Taken together, our results reveal that RKTG can modulate GPCR signaling through sequestering G to the Golgi apparatus and whereby attenuating the functions of G.
