Jiang Y, Xie X, Zhang Y, Luo X, Wang X, Fan F, Zheng D, Wang Z, Chen Y
Regulation of G protein signaling by RKTG via sequestrating Gbetagamma subunit to Golgi apparatus. [JOURNAL ARTICLE]
Mol Cell Biol 2009 Nov 2.
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 Galpha subunit from Gbetagamma subunit. While the Galpha subunit is imperative for downstream signaling, the Gbetagamma 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 Gbetagamma 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 Gbeta and tethers Gbetagamma to the Golgi. Overexpression of RKTG impedes the interaction of Gbetagamma with GRK2, abrogates the ligand-induced change of subcellular distribution of GRK2, reduces isoproterenol-stimulated phosphorylation of beta2-adrenergic receptor (beta2AR), and alters beta2AR desensitization. In addition, RKTG inhibits Gbetagamma- and ligand-mediated AKT that is enhanced in cells with downregulation of RKTG. Silencing of RKTG also enhances GRK2 internalization and compromises ligand-induced Gbeta translocation to the Golgi apparatus. Taken together, our results reveal that RKTG can modulate GPCR signaling through sequestering Gbetagamma to the Golgi apparatus and whereby attenuating the functions of Gbetagamma.
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