Evidence map›Paper›PMID 35594055›Full record

ArticleThe Biochemical journal2022

Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.

Xiaowen Duan, Dougall M Norris, Sean J Humphrey, Pengyi Yang, Kristen C Cooke, Will P Bultitude, Benjamin L Parker, Olivia J Conway, James G Burchfield, James R Krycer and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

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  6. Heliyon · 2025
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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

13 authors at 3 institutions in 2 countries.

Xiaowen DuanCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Dougall M NorrisMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, U.K.
Sean J HumphreyCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Pengyi YangCharles Perkins Centre, School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006, Australia.
Kristen C CookeCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Will P BultitudeResearch Department of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, U.K.
Benjamin L ParkerCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Olivia J ConwayMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, U.K.
James G BurchfieldCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
James R KrycerCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Frances M BrodskyResearch Department of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, U.K.
David E JamesCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Daniel J FazakerleyCharles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.ORCID 0000-0001-8241-2903
The University of Sydney · AUInstitute of Structural and Molecular Biology · GBWellcome/MRC Institute of Metabolic Science · GB

Funding

Medical Research Council MR/S007091/1Medical Research Council MR/S008144/1Wellcome TrustWellcome Trust 107858/Z/15/Z
6 · The paper itself

Abstract

Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.

Indexed as

Glycogen Synthase Kinase 3Phosphatidylinositol 3-KinasesAdipocytesAnimalsCell MembraneGlucoseGlucose Transporter Type 4HumansInsulinMicePhosphorylationProto-Oncogene Proteins c-aktSerineGlucoseGlucose Transporter Type 4Glycogen Synthase Kinase 3InsulinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSerineadipocytesglucose transportglycogen synthase kinaseinsulin signallingtrafficking regulator of GLUT4-1

Identifiers

PMID35594055
PMCPMC9284383
OpenAlexW4281263057

What OpenQuestion holds

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LicenceCC BY
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.