LKB1‐MARK2 signalling mediates lipopolysaccharide‐induced production of cytokines in mouse macrophages

Abstract 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.