Cargando…
Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP
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), gene...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696353/ https://www.ncbi.nlm.nih.gov/pubmed/31357561 http://dx.doi.org/10.3390/ijms20153677 |
_version_ | 1783444250698973184 |
---|---|
author | Sammel, Martin Peters, Florian Lokau, Juliane Scharfenberg, Franka Werny, Ludwig Linder, Stefan Garbers, Christoph Rose-John, Stefan Becker-Pauly, Christoph |
author_facet | Sammel, Martin Peters, Florian Lokau, Juliane Scharfenberg, Franka Werny, Ludwig Linder, Stefan Garbers, Christoph Rose-John, Stefan Becker-Pauly, Christoph |
author_sort | Sammel, Martin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6696353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66963532019-09-05 Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP Sammel, Martin Peters, Florian Lokau, Juliane Scharfenberg, Franka Werny, Ludwig Linder, Stefan Garbers, Christoph Rose-John, Stefan Becker-Pauly, Christoph Int J Mol Sci Article 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. MDPI 2019-07-26 /pmc/articles/PMC6696353/ /pubmed/31357561 http://dx.doi.org/10.3390/ijms20153677 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sammel, Martin Peters, Florian Lokau, Juliane Scharfenberg, Franka Werny, Ludwig Linder, Stefan Garbers, Christoph Rose-John, Stefan Becker-Pauly, Christoph Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title | Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title_full | Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title_fullStr | Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title_full_unstemmed | Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title_short | Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP |
title_sort | differences in shedding of the interleukin-11 receptor by the proteases adam9, adam10, adam17, meprin α, meprin β and mt1-mmp |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696353/ https://www.ncbi.nlm.nih.gov/pubmed/31357561 http://dx.doi.org/10.3390/ijms20153677 |
work_keys_str_mv | AT sammelmartin differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT petersflorian differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT lokaujuliane differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT scharfenbergfranka differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT wernyludwig differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT linderstefan differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT garberschristoph differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT rosejohnstefan differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp AT beckerpaulychristoph differencesinsheddingoftheinterleukin11receptorbytheproteasesadam9adam10adam17meprinameprinbandmt1mmp |