PXD002990-1

PXD002990 is an original dataset announced via ProteomeXchange.

Title	Complementary Phosphoproteomic Approaches Link IL-23R Downstream Signaling with Metabolic Adaptation in Lymphocytes
Description	Interleukin (IL)-23 mediated signal transduction represents a major molecular mechanism underlying the pathology of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). In addition, emerging evidence supports the role of IL-23-driven Th17 cells in inflammation. Components of the IL-23 signalling pathway, such as IL23R, JAK2 and STAT3, have been characterised, but elements unique to this network as compared to other interleukins have not been readily addressed. In this study, we have undertaken a multi-stage phosphoproteomics approach to better characterise downstream signalling events. To this end, we performed and compared phosphopeptide and phosphoprotein enrichment methodologies after activation of T lymphocytes by IL-23. We demonstrate the complementary nature of the two phosphor-enrichment approaches by maximising the capture of phosphorylation events. A total of 8069 unique phosphopeptides (containing 8344 unique sites), and 4317 unique phosphorylated proteins were identified, amongst which STAT3, PKM2, CDK6 and LASP-1 clearly showed induction of specific phosphorylation sites that were not readily observed after IL-2 stimulation. Interestingly, we observed subsequent translocation of STAT3 and PKM2 to the nucleus as well as increased phosphorylation especially of the nuclear portion at ~30 min after IL-23 stimulation, suggesting a wide range of cellular responses including proliferation and metabolic adaptation.
HostingRepository	PRIDE
AnnounceDate	2016-04-21
AnnouncementXML	Submission_2016-04-21_02:44:44.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD002990
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Phospho; Oxidation; Dimethyl; Dimethyl:2H(4); Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-30 01:12:41	ID requested
⏵ 1	2016-04-21 02:44:46	announced

Lochmatter C, Fischer R, Charles PD, Yu Z, Powrie F, Kessler BM, Integrative Phosphoproteomics Links IL-23R Signaling with Metabolic Adaptation in Lymphocytes. Sci Rep, 6():24491(2016) [pubmed]

curator keyword: Biological, Highlighted, Biomedical

submitter keyword: phosphoproteomics IL-23

Roman Fischer
contact affiliation	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002990
     1. Label: PRIDE project
     2. Name: Complementary Phosphoproteomic Approaches Link IL-23R Downstream Signaling with Metabolic Adaptation in Lymphocytes