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
Abstract
, 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.
Topics & Concepts
LYNInflammasomePhosphorylationCell biologySykTyrosine phosphorylationTyrosine kinaseSrc family kinaseProto-oncogene tyrosine-protein kinase SrcTyrosineChemistryBruton's tyrosine kinaseCaspase 1KinaseSignal transductionBiologyReceptorBiochemistryInflammasome and immune disordersinterferon and immune responses