Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome

Juan Tang; Yizhi Xiao; Guoxin Lin; Hui Guo; Han-Xiang Deng; Sha Tu; Wallace Y Langdon; Huixiang Yang; Lijian Tao; Yalan Li; R. Marshall Pope; Neetu Gupta; Jian Zhang

doi:10.1126/scisignal.abe3410

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Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome

Journal article

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Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome

Juan Tang, Yizhi Xiao, Guoxin Lin, Hui Guo, Han-Xiang Deng, Sha Tu, Wallace Y Langdon, Huixiang Yang, Lijian Tao, Yalan Li, …

Science signaling, Vol.14(706), pp.eabe3410-eabe3410

10/26/2021

DOI: 10.1126/scisignal.abe3410

PMID: 34699250

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https://admin.research-repository.uwa.edu.au/en/publications/55e9b90e-b32c-4109-a249-9c49ee07642aView

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Abstract

n response to microbes and other danger signals, the NLRP3 inflammasome in immune cells triggers the activation of the protease caspase-1, which mediates the maturation of the inflammatory cytokine IL-1β. Here, we investigated how the NLRP3 inflammasome is regulated. We found that its activation in primary mouse macrophages induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr918, which correlated with a subsequent increase in its ubiquitination that facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1β. Furthermore, mice lacking Lyn were more susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation is a prerequisite for the ubiquitination that dampens NLRP3 inflammasome activity.

Details

Title: Subtitle: Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome
Creators: Juan Tang - Central South University
Yizhi Xiao - University of Iowa
Guoxin Lin - University of Iowa
Hui Guo - University of Iowa
Han-Xiang Deng - Northwestern University
Sha Tu - University of Iowa
Wallace Y Langdon - The University of Western Australia
Huixiang Yang - Central South University
Lijian Tao - Central South University
Yalan Li - University of Iowa
R. Marshall Pope - University of Iowa
Neetu Gupta - Cleveland Clinic
Jian Zhang - University of Iowa
Resource Type: Journal article
Publication Details: Science signaling, Vol.14(706), pp.eabe3410-eabe3410
DOI: 10.1126/scisignal.abe3410
PMID: 34699250
NLM abbreviation: Sci Signal
ISSN: 1945-0877
eISSN: 1937-9145
Language: English
Date published: 10/26/2021
Academic Unit: Pathology; Medicine Administration
Record Identifier: 9984195071102771

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