Evidence map›Paper›PMID 33744286›Full record

ArticleThe Journal of biological chemistry

Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators.

Claire C Munier, Leonardo De Maria, Karl Edman, Anders Gunnarsson, Marianna Longo, Carol MacKintosh, Saleha Patel, Arjan Snijder, Lisa Wissler, Luc Brunsveld and 2 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

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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

12 authors at 5 institutions in 4 countries.

Claire C MunierResearch and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Eindhoven, The Netherlands.
Leonardo De MariaResearch and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Karl EdmanDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anders GunnarssonDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Marianna LongoDivision of Cell and Developmental Biology (C.M.), College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Carol MacKintoshDivision of Cell and Developmental Biology (C.M.), College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Saleha PatelDiscovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK.
Arjan SnijderDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Lisa WisslerDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Luc BrunsveldLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Eindhoven, The Netherlands.
Christian OttmannLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Eindhoven, The Netherlands.
Matthew W D PerryResearch and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Electronic address: Matthew.Perry@astrazeneca.com.
AstraZeneca (Sweden) · SEAstraZeneca (Netherlands) · NLEindhoven University of Technology · NLUniversity of Dundee · GBAstraZeneca (United Kingdom) · GB

Funding

Medical Research Council MC_EX_G0801767
6 · The paper itself

Abstract

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear. Hence, we sought to examine this system in more detail. We used phosphorylated GR peptides, biophysical studies, and X-ray crystallography to identify key residues within the ligand-binding domain of the GR, T524 and S617, whose phosphorylation results in binding of the representative 14-3-3 protein 14-3-3ζ. A kinase screen identified misshapen-like kinase 1 (MINK1) as responsible for phosphorylating T524 and Rho-associated protein kinase 1 for phosphorylating S617; cell-based approaches confirmed the importance of both GR phosphosites and MINK1 but not Rho-associated protein kinase 1 alone in inducing GR-14-3-3 binding. Together our results provide molecular-level insight into 14-3-3-mediated regulation of the GR and highlight both MINK1 and the GR-14-3-3 axis as potential targets for future therapeutic intervention.

Indexed as

Gene Expression Regulation14-3-3 ProteinsHEK293 CellsHumansMutationPhosphorylationProtein BindingProtein Serine-Threonine KinasesReceptors, GlucocorticoidThreonineTranscriptional Activation14-3-3 ProteinsMINK1 protein, humanProtein Serine-Threonine KinasesReceptors, GlucocorticoidThreonine14-3-3 proteinglucocorticoid receptorMINK1 kinasenuclear receptorphosphorylationprotein–protein interaction

Identifiers

PMID33744286
PMCPMC8080530
OpenAlexW3138466320

What OpenQuestion holds

Textmetadata
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.