| First Author | Lokau J | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 7 | Pages | 1761-1773 |
| PubMed ID | 26876177 | Mgi Jnum | J:384048 |
| Mgi Id | MGI:8327989 | Doi | 10.1016/j.celrep.2016.01.053 |
| Citation | Lokau J, et al. (2016) Proteolytic Cleavage Governs Interleukin-11 Trans-signaling. Cell Rep 14(7):1761-1773 |
| abstractText | Interleukin (IL)-11 has been shown to be a crucial factor for intestinal tumorigenesis, lung carcinomas, and asthma. IL-11 is thought to exclusively mediate its biological functions through cell-type-specific expression of the membrane-bound IL-11 receptor (IL-11R). Here, we show that the metalloprotease ADAM10, but not ADAM17, can release the IL-11R ectodomain. Chimeric proteins of the IL-11R and the IL-6 receptor (IL-6R) revealed that a small juxtamembrane portion is responsible for this substrate specificity of ADAM17. Furthermore, we show that the serine proteases neutrophil elastase and proteinase 3 can also cleave the IL-11R. The resulting soluble IL-11R (sIL-11R) is biologically active and binds IL-11 to activate cells. This IL-11 trans-signaling pathway can be inhibited specifically by the anti-inflammatory therapeutic compound sgp130Fc. In conclusion, proteolysis of the IL-11R represents a molecular switch that controls the IL-11 trans-signaling pathway and widens the number of cells that can be activated by IL-11. |
