ArticleThe Journal of biological chemistry2015
Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- RGS14 promotes the progression of hepatocellular carcinoma by activating the cAMP/PKA/CREB signaling pathway.Journal of cancer research and clinical oncology · 2025Article
- Noncanonical RGS14 structural determinants control hormone-sensitive NPT2A-mediated phosphate transport.The Biochemical journal · 2025Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Hepatic regulator of G protein signaling 14 ameliorates NAFLD through activating cAMP-AMPK signaling by targeting Giα1/3.Molecular metabolism · 2024Article
- Mechanisms of mGluR-dependent plasticity in hippocampal area CA2.Hippocampus · 2023Article
- RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.Hippocampus · 2023Review
- RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.The Journal of biological chemistry · 2022Article
- Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth.Nature communications · 2022Article
- RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures.Psychopharmacology · 2021Article
- RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.International journal of molecular sciences · 2021Review
- Intersection of two key signal integrators in the cell: activator of G-protein signaling 3 and dishevelled-2.Journal of cell science · 2020Article
- 14-3-3γ binds regulator of G protein signaling 14 (RGS14) at distinct sites to inhibit the RGS14:GαThe Journal of biological chemistry · 2018Article
- Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease.Pharmacological reviews · 2018Review
- Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (CaJournal of proteome research · 2018Article
- Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain.Brain structure & function · 2018Article
- The evolution of regulators of G protein signalling proteins as drug targets - 20 years in the making: IUPHAR Review 21.British journal of pharmacology · 2017Review
- Article
- Conformational insight into multi-protein signaling assemblies by hydrogen-deuterium exchange mass spectrometry.Current opinion in structural biology · 2016Review
- RGS14 regulates the lifetime of GPharmacology research & perspectives · 2016Article
- Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity.Molecular pharmacology · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
RGS14 contains distinct binding sites for both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits. The N-terminal regulator of G protein signaling (RGS) domain binds active Gαi/o-GTP, whereas the C-terminal G protein regulatory (GPR) motif binds inactive Gαi1/3-GDP. The molecular basis for how RGS14 binds different activation states of Gα proteins to integrate G protein signaling is unknown. Here we explored the intramolecular communication between the GPR motif and the RGS domain upon G protein binding and examined whether RGS14 can functionally interact with two distinct forms of Gα subunits simultaneously. Using complementary cellular and biochemical approaches, we demonstrate that RGS14 forms a stable complex with inactive Gαi1-GDP at the plasma membrane and that free cytosolic RGS14 is recruited to the plasma membrane by activated Gαo-AlF4(-). Bioluminescence resonance energy transfer studies showed that RGS14 adopts different conformations in live cells when bound to Gα in different activation states. Hydrogen/deuterium exchange mass spectrometry revealed that RGS14 is a very dynamic protein that undergoes allosteric conformational changes when inactive Gαi1-GDP binds the GPR motif. Pure RGS14 forms a ternary complex with Gαo-AlF4(-) and an AlF4(-)-insensitive mutant (G42R) of Gαi1-GDP, as observed by size exclusion chromatography and differential hydrogen/deuterium exchange. Finally, a preformed RGS14·Gαi1-GDP complex exhibits full capacity to stimulate the GTPase activity of Gαo-GTP, demonstrating that RGS14 can functionally engage two distinct forms of Gα subunits simultaneously. Based on these findings, we propose a working model for how RGS14 integrates multiple G protein signals in host CA2 hippocampal neurons to modulate synaptic plasticity.
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