ArticleScience signaling2015
Distinct profiles of functional discrimination among G proteins determine the actions of G protein-coupled receptors.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.
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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.
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Who cites it
183 citing papers in PubMed, 270 citations in OpenAlex.
- Innovative Approach Reveals How Receptors Control G Protein State Equilibria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- G protein signaling capabilities at the bradykinin 2 receptor.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Protein Frustration Reveals Orthosteric and Allosteric Active Sites in GPCR:G Protein Complexes.Journal of chemical information and modeling · 2026Article
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genome editing-based refinement of GPCR visualization in mice using the oxytocin receptor as a model.Scientific reports · 2026Article
- RGS proteins: Potential regulators of mouse melanopsin's signaling phototransduction cascade across ipRGC subtypes.Biophysical journal · 2026Article
- Allostery between Distant Structural Regions Dictates Selectivity in GPCR:G Protein Coupling.Biochemistry · 2026Article
- Novel GαGTP Sensors Reveal Endogenous and Subcellular G Protein Signaling Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Re-evaluating Gα protein-response element specificity in GPCR signaling.Communications biology · 2026Article
- Intracrine FFA4 signaling controls lipolysis at lipid droplets.Nature chemical biology · 2026Article
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- Ultra-large virtual screening unveils potent agonists of the neuromodulatory orphan receptor GPR139.Nature communications · 2025Article
- The ABCs of psychedelics: a preclinical roadmap for drug discovery.Trends in pharmacological sciences · 2025Review
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- Differential increase in endocannabinoid levels at the plasma and intracellular membranes.iScience · 2025Article
- Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.International journal of molecular sciences · 2025Review
- Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.Science advances · 2025Article
- Serotonin 5-HTACS chemical neuroscience · 2025Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Members of the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) family play key roles in many physiological functions and are extensively exploited pharmacologically to treat diseases. Many of the diverse effects of individual GPCRs on cellular physiology are transduced by heterotrimeric G proteins, which are composed of α, β, and γ subunits. GPCRs interact with and stimulate the binding of guanosine triphosphate (GTP) to the α subunit to initiate signaling. Mammalian genomes encode 16 different G protein α subunits, each one of which has distinct properties. We developed a single-platform, optical strategy to monitor G protein activation in live cells. With this system, we profiled the coupling ability of individual GPCRs for different α subunits, simultaneously quantifying the magnitude of the signal and the rates at which the receptors activated the G proteins. We found that individual receptors engaged multiple G proteins with varying efficacy and kinetics, generating fingerprint-like profiles. Different classes of GPCR ligands, including full and partial agonists, allosteric modulators, and antagonists, distinctly affected these fingerprints to functionally bias GPCR signaling. Finally, we showed that intracellular signaling modulators further altered the G protein-coupling profiles of GPCRs, which suggests that their differential abundance may alter signaling outcomes in a cell-specific manner. These observations suggest that the diversity of the effects of GPCRs on cellular physiology may be determined by their differential engagement of multiple G proteins, coupling to which produces signals with varying signal magnitudes and activation kinetics, properties that may be exploited pharmacologically.
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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.