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.