PXD022364

PXD022364 is an original dataset announced via ProteomeXchange.

Title	In vitro phosphorylated GR LBD LC-MSMS
Description	Glucocorticoid receptor (GR) is a ligand dependent transcription factor that plays a central role in inflammation. Part of a complex cellular network, GR activity is further modulated via protein–protein interactions . The regulation of GR by 14-3-3 proteins has been previously reported, though with differing sites of phosphorylation identified and variable consequences assigned. Hence, we sought to examine this protein–protein interaction and, using phosphorylated GR peptides, biophysical studies and X-ray crystallography, we identified key residues within the ligand binding domain of GR, T524 and S617, whose phosphorylation results in recognition by 14-3-3. Investigation of the kinases responsible for phosphorylation of these sites assigned a key role for MINK1 and cell-based approaches confirmed the importance of these two GR phosphosites and MINK1 in GR–14-3-3 binding. Together our results provide a molecular-level insight into 14-3-3 regulation of GR and highlight both MINK1 and the GR–14-3-3 axis as potential targets for future therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_13:45:54.915.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022364
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Claire Munier
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	SCIEX instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-05 00:27:45	ID requested
⏵ 1	2021-09-09 13:45:56	announced

Munier CC, De Maria L, Edman K, Gunnarsson A, Longo M, MacKintosh C, Patel S, Snijder A, Wissler L, Brunsveld L, Ottmann C, Perry MWD, Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators. J Biol Chem, 296():100551(2021) [pubmed]

submitter keyword: Glucocorticoid Receptor, Ligand Binding Domain, In vitro phosphorylation, ROCK1, MST1, MST2, MINK1, MAP4K4, LC-MSMS

Matthew W. D. Perry
contact affiliation	Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
contact email	Matthew.Perry@astrazeneca.com
lab head
Claire Munier
contact affiliation	Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
contact email	claire.munier@astrazeneca.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD022364

PRIDE project URI

• PRIDE
  1. PXD022364
     1. Label: PRIDE project
     2. Name: In vitro phosphorylated GR LBD LC-MSMS