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PXD014033 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProtein-tyrosine kinase 2-beta activates Interferon Regulatory Factor 5 to control inflammation
DescriptionInterferon regulatory factor 5 (IRF5) plays a distinct role in the regulation of immune responses in health and disease and is a genetic risk factor several autoimmune conditions, including systemic lupus erythematosus, diabetes, arthritis and inflammatory bowel disease. IRF5 function as a transcription factor requires post-translational modifications of the protein such as phosphorylation. Though several upstream signalling regulators of IRF5 have been identified, there is as yet little understanding of how they control IRF5 activity or whether other unknown kinases are involved. In this study, we systematically searched for IRF5 kinases using a reporter-based method for screening a library of 365 inhibitors of protein kinases. Based on the pool of the identified IRF5-inhibiting compounds we have compiled a list of putative IRF5 kinases, which we tested in subsequent in vitro assays. Protein-tyrosine kinase 2-beta (Ptk2b or PYK2) was one of the top hits, capable of binding to and phosphorylating mouse IRF5 at tyrosine (Y) 171. We have shown that IRF5 recruitment to target genes and IRF5-dependent transcription was impaired in cells treated with highly selective PYK2 inhibitors or in PYK2-deficient cells. Moreover, expression of pro-inflammatory cytokines was blocked in the supernatants of human biopsies from inflamed colon of patients with ulcerative colitis and treated ex vivo with a PYK2 inhibitor. Thus, we have identified a major role for PYK2 in regulating the inflammatory response and mapped its activity to the IRF5 innate sensing pathways.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRoman Fischer
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListAmmonia-loss; GG; Amidated; Isopropylphospho; Methyl; Oxidation; AEC-MAEC; Pro->pyro-Glu; Carboxy; Ethanedithiol; Propionamide; Phospho; Didehydro; Cation:Na; Deamidated; Trp->Kynurenin; Acetyl; Deoxy; Formyl; Carbamyl; HexNAc; Lys->Allysine; Carbamidomethyl; Cation:Ca[II]; Gln->pyro-Glu; Guanidinyl; Menadione-HQ; Glu->pyro-Glu; O-Methylphosphate; Ammonium; Dehydrated; Dimethyl; Biotin; Dioxidation; Hydroxymethyl; MercaptoEthanol; Carbofuran
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-05-28 01:52:09ID requested
12021-10-13 23:09:36announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: IRF5, PYK2
Contact List
Roman Fischer
contact affiliationDiscovery Proteomics Facility Oxford
contact emailroman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliationUniversity of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
dataset submitter
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