PXD028582 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-09-16 09:00:04 | ID requested | |
⏵ 1 | 2022-05-19 11:50:02 | announced | |
Publication List
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] |
Keyword List
submitter keyword: murine NLRP3 inflammasome, Lyn tryosine kinase, |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028582
- Label: PRIDE project
- Name: Tyrosine Phosphorylation of NLRP3 by Src Family Protein Tyrosine Kinase Lyn Suppresses NLRP3 Inflammasome Activation