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Regulation of G-Protein Signaling by RKTG via Sequestration of the Gβγ Subunit to the Golgi Apparatus
- Publication Year :
- 2010
- Publisher :
- American Society for Microbiology (ASM), 2010.
-
Abstract
- 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 betagamma subunit. While the G alpha subunit is imperative for downstream signaling, the G betagamma 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 betagamma 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 betagamma to the Golgi apparatus. Overexpression of RKTG impedes the interaction of G betagamma with GRK2, abrogates the ligand-induced change of subcellular distribution of GRK2, reduces isoproterenol-stimulated phosphorylation of the beta2-adrenergic receptor (beta 2AR), and alters beta 2AR desensitization. In addition, RKTG inhibits G betagamma- 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 betagamma to the Golgi apparatus and thereby attenuating the functions of G betagamma.
- Subjects :
- Protein subunit
Golgi Apparatus
GTP-Binding Protein beta Subunits
Saccharomyces cerevisiae
Biology
Ligands
Mice
symbols.namesake
GTP-Binding Protein gamma Subunits
Two-Hybrid System Techniques
Heterotrimeric G protein
Chlorocebus aethiops
Animals
Humans
Gene Silencing
Phosphorylation
Molecular Biology
Cells, Cultured
G protein-coupled receptor
G protein-coupled receptor kinase
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Articles
Cell Biology
Golgi apparatus
G-Protein-Coupled Receptor Kinases
Cell biology
Protein Transport
symbols
Receptors, Adrenergic, beta-2
Erratum
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....18084149900b5d84d3f7163e0c7a79aa