Biomol Screen Duncan I . Mackie and David L . Roman Protein Interaction Using AlphaScreen − RGS 17 Protein − α Development of a Novel High - Throughput Screen and Identification of Small - Molecule Inhibitors of the G
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A High Throughput Screen for RGS Proteins Using Steady State Monitoring of Free Phosphate Formation
G-protein coupled receptors are a diverse group that are the target of over 50% of marketed drugs. Activation of these receptors results in the exchange of bound GDP for GTP in the Gα subunit of the heterotrimeric G-protein. The Gα subunit dissociates from the β/γ subunits and both proceed to affect downstream signaling targets. The signal terminates by the hydrolysis of GTP to GDP and is tempo...
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Regulators of G-protein signaling (RGS) proteins are important components of signal transduction pathways initiated through G-protein-coupled receptors (GPCRs). RGS proteins accelerate the intrinsic GTPase activity of G-protein alpha-subunits (Galpha) and thus shorten the time course and reduce the magnitude of G-protein alpha- and betagamma-subunit signaling. Inhibiting RGS action has been pro...
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Regulators of G protein signaling (RGS) proteins are potent negative modulators of G protein signaling and have been proposed as potential targets for small-molecule inhibitor development. We report a high-throughput time-resolved fluorescence resonance energy transfer screen to identify inhibitors of RGS4 and describe the first reversible small-molecule inhibitors of an RGS protein. Two closel...
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Ligands for G-protein-coupled receptors (GPCRs) represent approximately 50% of currently marketed drugs. Regulators of G Protein Signaling (RGS) proteins modulate heterotrimeric G proteins and, thus, GPCR signaling, by accelerating the intrinsic GTPase activity of the G subunit. Given the prevalence of GPCR targeted therapeutics and the role RGS proteins play in G protein signaling, some RGS p...
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To study the biology of regulators of G-protein signaling (RGS) proteins and to facilitate the identification of small molecule modulators of RGS proteins, the authors recently developed an advanced yeast 2-hybrid (YTH) assay format for GalphaZ and RGS-Z1. Moreover, they describe the development of a multiplexed luciferase-based assay that has been successfully adapted to screen large numbers o...
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