| First Author | Roh KH | Year | 2021 |
| Journal | Cell Mol Life Sci | Volume | 78 |
| Issue | 5 | Pages | 2315-2328 |
| PubMed ID | 32975614 | Mgi Jnum | J:319405 |
| Mgi Id | MGI:6823265 | Doi | 10.1007/s00018-020-03650-4 |
| Citation | Roh KH, et al. (2021) TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-kappaB signaling pathway in macrophages. Cell Mol Life Sci 78(5):2315-2328 |
| abstractText | Pattern-recognition receptors including Toll-like receptors (TLRs) recognize invading pathogens and trigger an immune response in mammals. Here we show that mammalian ste20-like kinase 1/serine/threonine kinase 4 (MST1/STK4) functions as a negative regulator of lipopolysaccharide (LPS)-induced activation of the TLR4-NF-kappaB signaling pathway associated with inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased the susceptibility of mice to LPS-induced septic shock. Ablation of MST1/STK4 also enhanced NF-kappaB activation triggered by LPS in bone marrow-derived macrophages (BMDMs), leading to increased production of proinflammatory cytokines by these cells. Furthermore, MST1/STK4 inhibited TRAF6 autoubiquitination as well as TRAF6-mediated downstream signaling induced by LPS. In addition, we found that TRAF6 mediates the LPS-induced activation of MST1/STK4 by catalyzing its ubiquitination, resulting in negative feedback regulation by MST1/STK4 of the LPS-induced pathway leading to cytokine production in macrophages. Together, our findings suggest that MST1/STK4 functions as a negative modulator of the LPS-induced NF-kappaB signaling pathway during macrophage activation. |
