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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In 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.

Original languageEnglish (US)
Article numberabe3410
JournalScience Signaling
Volume14
Issue number706
DOIs
StatePublished - Oct 26 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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