Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages

• DOI: 10.1038/ncomms8167
• Publication Date: 2015-05-18T09:13:11Z
• Authors: Mingyue Wen; Xianwei Ma; Hong Cheng; Wei Jiang; Xiongfei Xu; Yi Zhang; Yan Zhang; Zhenhong Guo; Yizhi Yu; Hongmei Xu; Cheng Qian; Xuetao Cao; Huazhang An
• Keywords: TLR9

NDR/LATS kinase family is highly conserved from yeast to human. It remains unknown whether the members of this function in innate immune responses. Here we demonstrate that Stk38 negatively regulates TLR9-mediated responses macrophages. constitutively associates with ubiquitin E3 ligase Smurf1, and facilitates Smurf1-mediated MEKK2 ubiquitination degradation. required for CpG-induced ERK1/2 activation, TNF-α IL-6 production but not LPS-induced production. Accordingly, deficiency increases without significantly affecting Stk38-deficient mice produce more IL-6, display increased lethality than control wild-type upon E. coli infection. are also susceptible CLP-induced sepsis mice. Thus, important limiting inflammatory cytokine necessary protecting host injury during infection, possibly by regulating TLR9 signalling.