PXD036995-1

PXD036995 is an original dataset announced via ProteomeXchange.

Title	Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation
Description	Receptor-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.
HostingRepository	PRIDE
AnnounceDate	2022-10-12
AnnouncementXML	Submission_2022-10-12_08:46:30.489.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	HailinTu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-25 15:08:05	ID requested
⏵ 1	2022-10-12 08:46:30	announced

Dataset with its publication pending

submitter keyword: inflammation, phosphorylation,RIPK1, cell death

XinLin
contact affiliation	Institute for Immunology, School of Medicine, Tsinghua University, Beijing, China.
contact email	linxin307@tsinghua.edu.cn
lab head
HailinTu
contact affiliation	Tsinghua University
contact email	helentoo1994@gmail.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/2022/10/PXD036995

PRIDE project URI

• PRIDE
  1. PXD036995
     1. Label: PRIDE project
     2. Name: Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation