ArticleThe Journal of biological chemistry2011
G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Regulator of G protein signalling 14 (RGS14) protein expression profile in the adult mouse brain.The European journal of neuroscience · 2024Article
- Hepatic regulator of G protein signaling 14 ameliorates NAFLD through activating cAMP-AMPK signaling by targeting Giα1/3.Molecular metabolism · 2024Article
- RGS14 limits seizure-induced mitochondrial oxidative stress and pathology in hippocampus.Neurobiology of disease · 2023Article
- RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.Hippocampus · 2023Review
- RGS14 is neuroprotective against seizure-induced mitochondrial oxidative stress and pathology in hippocampus.bioRxiv : the preprint server for biology · 2023Article
- RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.The Journal of biological chemistry · 2022Article
- RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.International journal of molecular sciences · 2021Review
- Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.Cell communication and signaling : CCS · 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
- Article
- RGS14 regulates the lifetime of GPharmacology research & perspectives · 2016Article
- Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o.The Biochemical journal · 2016Article
- Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity.Molecular pharmacology · 2016Review
- Direct Coupling of a Seven-Transmembrane-Span Receptor to a Gαi G-Protein Regulatory Motif Complex.Molecular pharmacology · 2015Article
- Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).The Journal of biological chemistry · 2015Article
- Bioluminescence resonance energy transfer to detect protein-protein interactions in live cells.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad.Molecular pharmacology · 2014Review
- Article
- G protein coupled receptor signaling complexes in live cells.Cellular logistics · 2014Article
- Translocation of activator of G-protein signaling 3 to the Golgi apparatus in response to receptor activation and its effect on the trans-Golgi network.The Journal of biological chemistry · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Regulator of G protein Signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates both conventional and unconventional G protein signaling pathways. Like other RGS (regulator of G protein signaling) proteins, RGS14 acts as a GTPase accelerating protein to terminate conventional Gα(i/o) signaling. However, unlike other RGS proteins, RGS14 also contains a G protein regulatory/GoLoco motif that specifically binds Gα(i1/3)-GDP in cells and in vitro. The non-receptor guanine nucleotide exchange factor Ric-8A can bind and act on the RGS14·Gα(i1)-GDP complex to play a role in unconventional G protein signaling independent of G protein-coupled receptors (GPCRs). Here we demonstrate that RGS14 forms a Gα(i/o)-dependent complex with a G(i)-linked GPCR and that this complex is regulated by receptor agonist and Ric-8A (resistance to inhibitors of cholinesterase-8A). Using live cell bioluminescence resonance energy transfer, we show that RGS14 functionally associates with the α(2A)-adrenergic receptor (α(2A)-AR) in a Gα(i/o)-dependent manner. This interaction is markedly disrupted after receptor stimulation by the specific agonist UK14304, suggesting complex dissociation or rearrangement. Agonist-mediated dissociation of the RGS14·α(2A)-AR complex occurs in the presence of Gα(i/o) but not Gα(s) or Gα(q). Unexpectedly, RGS14 does not dissociate from Gα(i1) in the presence of stimulated α(2A)-AR, suggesting preservation of RGS14·Gα(i1) complexes after receptor activation. However, Ric-8A facilitates dissociation of both the RGS14·Gα(i1) complex and the Gα(i1)-dependent RGS14·α(2A)-AR complex after receptor activation. Together, these findings indicate that RGS14 can form complexes with GPCRs in cells that are dependent on Gα(i/o) and that these RGS14·Gα(i1)·GPCR complexes may be substrates for other signaling partners such as Ric-8A.
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