期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 30, 期 1, 页码 78-90出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01038-09
关键词
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资金
- Chinese Academy of Sciences [KSCX1-YW-02]
- National Natural Science Foundation of China [30588002, 30830037]
- Science & Technology Commission of Shanghai Municipality [75407001]
- Ministry of Science and Technology of China [2007CB947100, 2006CB943900]
Upon ligand binding, G-protein-coupled receptors (GPCRs) impart the signal to heterotrimeric G proteins composed of alpha, beta, and gamma subunits, leading to dissociation of the G alpha subunit from the G beta gamma subunit. While the G alpha subunit is imperative for downstream signaling, the G beta gamma subunit, in its own right, mediates a variety of cellular responses such as GPCR desensitization via recruiting GRK to the plasma membrane and AKT stimulation. Here we report a mode of spatial regulation of the G beta gamma subunit through alteration in subcellular compartmentation. RKTG (Raf kinase trapping to Golgi apparatus) is a newly characterized membrane protein specifically localized at the Golgi apparatus. The N terminus of RKTG interacts with G beta and tethers G beta gamma to the Golgi apparatus. Overexpression of RKTG impedes the interaction of G beta gamma with GRK2, abrogates the ligand-induced change of subcellular distribution of GRK2, reduces isoproterenol-stimulated phosphorylation of the beta 2-adrenergic receptor (beta 2AR), and alters beta 2AR desensitization. In addition, RKTG inhibits G beta gamma- and ligand-mediated AKT phosphorylation that is enhanced in cells with downregulation of RKTG. Silencing of RKTG also alters GRK2 internalization and compromises ligand-induced G beta translocation to the Golgi apparatus. Taken together, our results reveal that RKTG can modulate GPCR signaling through sequestering G beta gamma to the Golgi apparatus and thereby attenuating the functions of G beta gamma.
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