Open AccessLKB1‐MARK2 signalling mediates lipopolysaccharide‐induced production of cytokines in mouse macrophages
Author(s) -
Deng Jie,
Wen Chunmei,
Ding Xiangyu,
Zhang Xi,
Hou Guoqing,
Liu Andong,
Xu Hui,
Cao Xuan,
Bai Yongheng
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15710
Subject(s) - lipopolysaccharide , phosphoproteomics , phosphorylation , signalling , immunology , macrophage , proinflammatory cytokine , microbiology and biotechnology , biology , inflammation , innate immune system , tumor necrosis factor alpha , immune system , protein phosphorylation , protein kinase a , in vitro , biochemistry
Lipopolysaccharide (LPS) is an endotoxin involved in a number of acute and chronic inflammatory syndromes. Although LPS‐induced signalling has been extensively studied, there are still mysteries remaining to be revealed. In the current study, we used high‐throughput phosphoproteomics to profile LPS‐initiated signalling and aimed to find novel mediators. A total of 448 phosphoproteins with 765 phosphorylation sites were identified, and we further validated that the phosphorylation of MARK2 on T208 was important for the regulation on LPS‐induced CXCL15 (human IL‐8 homolog), IL‐1β, IL‐6 and TNF‐α release, in which LKB1 had a significant contribution. In summary, induction of cytokines by LPS in mouse macrophage is regulated by LKB1‐MARK2 signals. Our study provides new clues for further exploring the underlying mechanisms of LPS‐induced diseases, and new therapeutic approaches concerning bacterial infection may be derived from these findings.