ArticleThe Journal of biological chemistry2010
G proteins in reverse mode: receptor-mediated GTP release inhibits G protein and effector function.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Innovative Approach Reveals How Receptors Control G Protein State Equilibria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterization of the GTPγS release function of a G protein-coupled receptor.Nature communications · 2025Article
- Membrane disruption attenuates agonist potency in prostanoid receptors.The Biochemical journal · 2025Article
- The guanine nucleotide exchange factor Ric-8A regulates the sensitivity of constitutively active Gαq to the inhibitor YM-254890.The Journal of biological chemistry · 2025Article
- Heterotrimeric GThe Journal of biological chemistry · 2020Review
- cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology-tribute to Karl H. Jakobs.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Lifetime of muscarinic receptor-G-protein complexes determines coupling efficiency and G-protein subtype selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Dissociated GαGTP and Gβγ protein subunits are the major activated form of heterotrimeric Gi/o proteins.The Journal of biological chemistry · 2014Article
- Optogenetic reporters: Fluorescent protein-based genetically encoded indicators of signaling and metabolism in the brain.Progress in brain research · 2012Review
- Autocrine signaling via A(1) adenosine receptors causes downregulation of M(2) receptors in adult rat atrial myocytes in vitro.Pflugers Archiv : European journal of physiology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Active G protein-coupled receptors activate heterotrimeric Galphabetagamma proteins by catalyzing the exchange of GDP by GTP at the Galpha subunit. A paradoxical attenuation of G protein-activated inwardly rectifying potassium channels (GIRK) upon stimulation of native cells with high concentrations of agonist is known. However, a deactivation of activated G proteins by active receptors has not been experimentally studied in intact cells. We monitored GIRK currents and G(o) protein activation by means of fluorescence resonance energy transfer (FRET) in parallel. The results suggested that GIRK currents were paradoxically attenuated due to an inactivation of G(o) proteins by active alpha(2A)-adrenergic receptors. To study the mechanisms, G protein activation and receptor-G protein interactions were analyzed as a function of nucleotide type and nucleotide concentrations by means of FRET, while controlling intracellular nucleotides upon permeabilization of the cell membrane. Results suggested a receptor-catalyzed dissociation of GTP from activated heterotrimeric Galphabetagamma. Consequently, nucleotide-free G proteins were sequestrated in heterotrimeric conformation at the active receptor, thus attenuating downstream signaling in an agonist-dependent manner.
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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.