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- Title
Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP.
- Authors
Sammel, Martin; Peters, Florian; Lokau, Juliane; Scharfenberg, Franka; Werny, Ludwig; Linder, Stefan; Garbers, Christoph; Rose-John, Stefan; Becker-Pauly, Christoph
- Abstract
Interleukin-11 (IL-11) has been associated with inflammatory conditions, bone homeostasis, hematopoiesis, and fertility. So far, these functions have been linked to classical IL-11 signaling via the membrane bound receptor (IL-11R). However, a signaling cascade via the soluble IL-11R (sIL-11R), generated by proteolytic cleavage, can also be induced. This process is called IL-11 trans-signaling. A disintegrin and metalloprotease 10 (ADAM10) and neutrophil elastase were described as ectodomain sheddases of the IL-11R, thereby inducing trans-signaling. Furthermore, previous studies employing approaches for the stimulation and inhibition of endogenous ADAM-proteases indicated that ADAM10, but not ADAM17, can cleave the IL-11R. Herein, we show that several metalloproteases, namely ADAM9, ADAM10, ADAM17, meprin β, and membrane-type 1 matrix metalloprotease/matrix metalloprotease-14 (MT1-MMP/MMP-14) when overexpressed are able to shed the IL-11R. All sIL-11R ectodomains were biologically active and capable of inducing signal transducer and activator of transcription 3 (STAT3) phosphorylation in target cells. The difference observed for ADAM10/17 specificity compared to previous studies can be explained by the different approaches used, such as stimulation of protease activity or making use of cells with genetically deleted enzymes.
- Subjects
PROTEOLYTIC enzymes; LEUCOCYTE elastase; ELASTASES; METALLOPROTEINASES; HEMATOPOIESIS
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 15, p3677
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20153677