Evidence map›Paper›PMID 23250758›Full record

ArticleThe Journal of biological chemistry2013

Assembly and function of the regulator of G protein signaling 14 (RGS14)·H-Ras signaling complex in live cells are regulated by Gαi1 and Gαi-linked G protein-coupled receptors.

Christopher P Vellano, Nicole E Brown, Joe B Blumer, John R Hepler

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 47 citations in OpenAlex.

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  17. RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.International journal of molecular sciences · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Christopher P VellanoDepartment of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Nicole E Brown
Joe B Blumer
John R Hepler
Emory University · USMedical University of South Carolina · US

Funding

Structure and Function of the G-alpha-i1:RGS14:H-Ras signaling complexR01NS037112 · NINDS · EMORY UNIVERSITY · PI HEPLER, JOHN R · 1998 to 2023
$7.2M
ENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8M
Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
RGS Protein Regulation of G Protein Coupled ReceptorsR01NS049195 · NINDS · EMORY UNIVERSITY · PI HEPLER, JOHN R · 2006 to 2010
$1.7M
AGS4 in G-protein Signal ProcessingR01GM086510 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BLUMER, JOE B · 2009 to 2013
$1.5M
NIGMS NIH HHS GM086510NIGMS NIH HHS R01 GM086510NIGMS NIH HHS T32 GM008602NINDS NIH HHS P30 NS055077NINDS NIH HHS P30NS055077NINDS NIH HHS R01 NS037112NINDS NIH HHS R01NS037112NINDS NIH HHS R01 NS049195NINDS NIH HHS R01NS049195
6 · The paper itself

Abstract

Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates heterotrimeric G protein and H-Ras signaling pathways. RGS14 possesses an RGS domain that binds active Gα(i/o)-GTP subunits to promote GTP hydrolysis and a G protein regulatory (GPR) motif that selectively binds inactive Gα(i1/3)-GDP subunits to form a stable heterodimer at cellular membranes. RGS14 also contains two tandem Ras/Rap binding domains (RBDs) that bind H-Ras. Here we show that RGS14 preferentially binds activated H-Ras-GTP in live cells to enhance H-Ras cellular actions and that this interaction is regulated by inactive Gα(i1)-GDP and G protein-coupled receptors (GPCRs). Using bioluminescence resonance energy transfer (BRET) in live cells, we show that RGS14-Luciferase and active H-Ras(G/V)-Venus exhibit a robust BRET signal at the plasma membrane that is markedly enhanced in the presence of inactive Gα(i1)-GDP but not active Gα(i1)-GTP. Active H-Ras(G/V) interacts with a native RGS14·Gα(i1) complex in brain lysates, and co-expression of RGS14 and Gα(i1) in PC12 cells greatly enhances H-Ras(G/V) stimulatory effects on neurite outgrowth. Stimulation of the Gα(i)-linked α(2A)-adrenergic receptor induces a conformational change in the Gα(i1)·RGS14·H-Ras(G/V) complex that may allow subsequent regulation of the complex by other binding partners. Together, these findings indicate that inactive Gα(i1)-GDP enhances the affinity of RGS14 for H-Ras-GTP in live cells, resulting in a ternary signaling complex that is further regulated by GPCRs.

Indexed as

AnimalsCell MembraneCell SurvivalGTP-Binding Protein alpha Subunits, Gi-GoHEK293 CellsHumansMiceModels, BiologicalNeuritesPC12 CellsProtein BindingProtein Structure, TertiaryProtein TransportProto-Oncogene Proteins p21(ras)RatsReceptors, Adrenergic, alpha-2Gnai1 protein, mouseGnai1 protein, ratGTP-Binding Protein alpha Subunits, Gi-GoHras protein, mouseProto-Oncogene Proteins p21(ras)Receptors, Adrenergic, alpha-2Receptors, Adrenergic, beta-2Rgs14 protein, mouseRgs14 protein, ratRGS Proteins

Identifiers

PMID23250758
PMCPMC3561580
OpenAlexW1983228276

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.