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Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor.

ABSTRACT: G-protein signaling modulators (GPSM) play diverse functional roles through their interaction with G-protein subunits. AGS3 (GPSM1) contains four G-protein regulatory motifs (GPR) that directly bind G?(i) free of G?? providing an unusual scaffold for the "G-switch" and signaling complexes, but the mechanism by which signals track into this scaffold are not well understood. We report the regulation of the AGS3·G?(i) signaling module by a cell surface, seven-transmembrane receptor. AGS3 and G?(i1) tagged with Renilla luciferase or yellow fluorescent protein expressed in mammalian cells exhibited saturable, specific bioluminescence resonance energy transfer indicating complex formation in the cell. Activation of ?(2)-adrenergic receptors or ?-opioid receptors reduced AGS3-RLuc·G?(i1)-YFP energy transfer by over 30%. The agonist-mediated effects were inhibited by pertussis toxin and co-expression of RGS4, but were not altered by G?? sequestration with the carboxyl terminus of GRK2. G?(i)-dependent and agonist-sensitive bioluminescence resonance energy transfer was also observed between AGS3 and cell-surface receptors typically coupled to G?(i) and/or G?(o) indicating that AGS3 is part of a larger signaling complex. Upon receptor activation, AGS3 reversibly dissociates from this complex at the cell cortex. Receptor coupling to both G??? and GPR-G?(i) offer additional flexibility for systems to respond and adapt to challenges and orchestrate complex behaviors.

SUBMITTER: Oner SS

PROVIDER: S-EPMC2962495 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor.

Oner Sukru Sadik SS An Ningfei N Vural Ali A Breton Billy B Bouvier Michel M Blumer Joe B JB Lanier Stephen M SM

The Journal of biological chemistry 20100817 44

G-protein signaling modulators (GPSM) play diverse functional roles through their interaction with G-protein subunits. AGS3 (GPSM1) contains four G-protein regulatory motifs (GPR) that directly bind Gα(i) free of Gβγ providing an unusual scaffold for the "G-switch" and signaling complexes, but the mechanism by which signals track into this scaffold are not well understood. We report the regulation of the AGS3·Gα(i) signaling module by a cell surface, seven-transmembrane receptor. AGS3 and Gα(i1) ...[more]

PMID: 20716524

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Dataset Information

Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor.

Publications

Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor.

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