PXD028582

PXD028582 is an original dataset announced via ProteomeXchange.

Title	Tyrosine Phosphorylation of NLRP3 by Src Family Protein Tyrosine Kinase Lyn Suppresses NLRP3 Inflammasome Activation
Description	The NLRP3 inflammasome is a multi-protein complex that triggers the activation of the inflammatory protein caspase-1 and the maturation of the cytokine IL-1 in response to microbes and other danger signals in host cells. Here, we sought a deeper understanding of how the NLRP3 inflammasome is regulated. We found that inflammasome activation induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr918, and that this phosphorylation of NLRP3 correlated with a subsequent increase in its ubiquitination, which facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1. Furthermore, mice lacking Lyn were highly susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation of NLRP3 is a prerequisite for its ubiquitination, thus dampening NLRP3 inflammasome activity.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_11:50:01.626.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028582
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	robert Pope
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 09:00:04	ID requested
⏵ 1	2022-05-19 11:50:02	announced

Tang J, Xiao Y, Lin G, Guo H, Deng HX, Tu S, Langdon WY, Yang H, Tao L, Li Y, Pope RM, Gupta N, Zhang J, Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome. Sci Signal, 14(706):eabe3410(2021) [pubmed]

submitter keyword: murine NLRP3 inflammasome, Lyn tryosine kinase,

Jian Zhang, M.D.
contact affiliation	Professor of Pathology Endowed Chair in Immunology Research University of Iowa Health Care Distinguished Scholar Department of Pathology The University of Iowa Tel: 319-335-1121 (O)/319-335-0990 (Lab)
contact email	Jiang-zhang@uiowa.edu
lab head
robert Pope
contact affiliation	University of Iowa, COM, Iowa City, IA 52241
contact email	marshall-pope@uiowa.edu
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/2022/05/PXD028582

PRIDE project URI

• PRIDE
  1. PXD028582
     1. Label: PRIDE project
     2. Name: Tyrosine Phosphorylation of NLRP3 by Src Family Protein Tyrosine Kinase Lyn Suppresses NLRP3 Inflammasome Activation