title: Regulation of the subcellular localization of the G-protein subunit regulator GPSM3 through direct association with 14-3-3 protein.
abstract: G-protein signaling modulator-3 (GPSM3), also known as G18 or AGS4, is a member of the Gα(i/o)-Loco (GoLoco) motif containing proteins. GPSM3 acts through its two GoLoco motifs to exert GDP dissociation inhibitor activity over Gα(i) subunits; recently revealed is the existence of an additional regulatory site within GPSM3 directed toward monomeric Gβ subunits during their biosynthesis. Here, using in silico and proteomic approaches, we have found that GPSM3 also interacts directly with numerous members of the 14-3-3 protein family. This interaction is dependent on GPSM3 phosphorylation, creating a mode II consensus 14-3-3 binding site. 14-3-3 binding to the N-terminal disordered region of GPSM3 confers stabilization from protein degradation. The complex of GPSM3 and 14-3-3 is exclusively cytoplasmic, and both moieties mutually control their exclusion from the nucleus. Phosphorylation of GPSM3 by a proline-directed serine/threonine kinase and the resultant association of 14-3-3 is the first description of post-translational regulation of GPSM3 subcellular localization, a process that likely regulates important spatio-temporal aspects of G-protein-coupled receptor signaling modulation by GPSM3.
authors: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7365, USA.
authors: Patrick M
authors: PM
authors: Giguère
authors: Geneviève
authors: G
authors: Laroche
authors: Emily A
authors: EA
authors: Oestreich
authors: Joseph A
authors: JA
authors: Duncan
authors: David P
authors: DP
authors: Siderovski
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D055550:Protein Stability; D021381:Protein Transport / Q000502:physiology; D059748:Proteolysis; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins; C487218:GPSM3 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go