| Literature DB >> 26876177 |
Juliane Lokau1, Rebecca Nitz2, Maria Agthe1, Niloufar Monhasery2, Samadhi Aparicio-Siegmund1, Neele Schumacher1, Janina Wolf1, Katja Möller-Hackbarth1, Georg H Waetzig3, Joachim Grötzinger1, Gerhard Müller-Newen4, Stefan Rose-John1, Jürgen Scheller5, Christoph Garbers6.
Abstract
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.Entities:
Keywords: ADAM10; ADAM17; interleukin-11; proteolysis; signal transduction
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Year: 2016 PMID： 26876177 DOI： 10.1016/j.celrep.2016.01.053
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423