ArticleJournal of biomolecular screening2009
Two Galpha(i1) rate-modifying mutations act in concert to allow receptor-independent, steady-state measurements of RGS protein activity.
Article in Journal of biomolecular screening, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits.Molecular cell · 2023Article
- High-resolution structure of RGS17 suggests a role for CaThe Journal of biological chemistry · 2019Article
- G-Protein Signaling Protein-17 (RGS17) Is Upregulated and Promotes Tumor Growth and Migration in Human Colorectal Carcinoma.Oncology research · 2018Article
- Mechanism of the intrinsic arginine finger in heterotrimeric G proteins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A Homogenous Bioluminescent System for Measuring GTPase, GTPase Activating Protein, and Guanine Nucleotide Exchange Factor Activities.Assay and drug development technologies · 2015Article
- Integration of Fourier Transform Infrared Spectroscopy, Fluorescence Spectroscopy, Steady-state Kinetics and Molecular Dynamics Simulations of Gαi1 Distinguishes between the GTP Hydrolysis and GDP Release Mechanism.The Journal of biological chemistry · 2015Article
- Discovery of MINC1, a GTPase-activating protein small molecule inhibitor, targeting MgcRacGAP.Combinatorial chemistry & high throughput screening · 2015Article
- Current approaches for the discovery of drugs that deter substance and drug abuse.Expert opinion on drug discovery · 2014Review
- RGS21, a regulator of taste and mucociliary clearance?The Laryngoscope · 2014Article
- Modification and functional inhibition of regulator of G-protein signaling 4 (RGS4) by 4-hydroxy-2-nonenal.Chemical research in toxicology · 2013Article
- Reversible inhibitors of regulators of G-protein signaling identified in a high-throughput cell-based calcium signaling assay.Cellular signalling · 2013Article
- Domain-opening and dynamic coupling in the α-subunit of heterotrimeric G proteins.Biophysical journal · 2013Article
- RGS17: an emerging therapeutic target for lung and prostate cancers.Future medicinal chemistry · 2013Article
- A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation.PloS one · 2013Article
- Evaluating modulators of "Regulator of G-protein Signaling" (RGS) proteins.Current protocols in pharmacology · 2012Article
- GDP release preferentially occurs on the phosphate side in heterotrimeric G-proteins.PLoS computational biology · 2012Article
- Fluorescence detection of GDP in real time with the reagentless biosensor rhodamine-ParM.The Biochemical journal · 2011Article
- Regulators of G-protein signaling and their Gα substrates: promises and challenges in their use as drug discovery targets.Pharmacological reviews · 2011Review
- Fluorescence polarization assays in small molecule screening.Expert opinion on drug discovery · 2011Article
- A homogeneous method to measure nucleotide exchange by α-subunits of heterotrimeric G-proteins using fluorescence polarization.Assay and drug development technologies · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
RGS proteins are critical modulators of G-protein-coupled receptor (GPCR) signaling given their ability to deactivate Galpha subunits via GTPase-accelerating protein (GAP) activity. Their selectivity for specific GPCRs makes them attractive therapeutic targets. However, measuring GAP activity is complicated by slow guanosine diphosphate (GDP) release from Galpha and lack of solution phase assays for detecting free GDP in the presence of excess guanosine triphosphate (GTP). To overcome these hurdles, the authors developed a Galpha(i1) mutant with increased GDP dissociation and decreased GTP hydrolysis rates, enabling detection of GAP activity using steady-state GTP hydrolysis. Galpha(i1)(R178M/A326S) GTPase activity was stimulated 6- to 12-fold by RGS proteins known to act on Galpha(i) subunits and not affected by those unable to act on Galpha(i), demonstrating that the Galpha/RGS domain interaction selectivity was not altered by mutation. The selectivity and affinity of Galpha( i1)(R178M/A326S) interaction with RGS proteins was confirmed by molecular binding studies. To enable nonradioactive, homogeneous detection of RGS protein effects on Galpha(i1)(R178M/A326S), the authors developed a Transcreener fluorescence polarization immunoassay based on a monoclonal antibody that recognizes GDP with greater than 100-fold selectivity over GTP. Combining Galpha(i1)(R178M/A326S) with a homogeneous, fluorescence-based GDP detection assay provides a facile means to explore the targeting of RGS proteins as a new approach for selective modulation of GPCR signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.