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PXD036995-1

PXD036995 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation
DescriptionReceptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a cytosolic protein kinase that regulates multiple inflammatory and cell death pathways. Serine/Threonine phosphorylation of RIPK1 is known to suppress RIPK1 kinase-mediated cell death in the contexts of inflammation, infection and embryogenesis, however, regulation by tyrosine phosphorylation has not been reported. Here, we show that non-receptor tyrosine kinases Janus kinase 1 (JAK1) and SRC are able to phosphorylate RIPK1 at Y384 (Y383 in murine RIPK1), leading to suppression of TNF-induced cell death. Mice bearing a homozygous Ripk1 mutation that prevents tyrosine phosphorylation of RIPK1 (Ripk1Y383F/Y383F), develop systemic inflammation and emergency haematopoiesis. Mechanistically, Ripk1Y383F/Y383F mutation promotes RIPK1 kinase activation and enhances TNF-induced apoptosis and necroptosis, which is partially due to impaired recruitment and activation of MAP kinase-activated protein kinase 2 (MK2). The systemic inflammation and emergency haematopoiesis in Ripk1Y383F/Y383F mice are largely alleviated by RIPK1 kinase inhibition, and prevented by genomic deletions targeted to the upstream pathway (either to Tumor necrosis factor receptor 1 or RIPK3 and Caspase8 simultaneously). In summary, our results demonstrate that tyrosine phosphorylation of RIPK1 is critical for regulating RIPK1 activity to limit cell death and inflammation.
HostingRepositoryPRIDE
AnnounceDate2022-10-12
AnnouncementXMLSubmission_2022-10-12_08:46:30.489.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHailinTu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-25 15:08:05ID requested
12022-10-12 08:46:30announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: inflammation, phosphorylation,RIPK1, cell death
Contact List
XinLin
contact affiliationInstitute for Immunology, School of Medicine, Tsinghua University, Beijing, China.
contact emaillinxin307@tsinghua.edu.cn
lab head
HailinTu
contact affiliationTsinghua University
contact emailhelentoo1994@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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