MCB Accepts, published online ahead of print on 2 November 2009

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Mol. Cell. Biol. doi:10.1128/MCB.01038-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

^* To whom correspondence should be addressed. Email: ychen3{at}sibs.ac.cn.

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 G and 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.