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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...

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Autores principales: Sammel, Martin, Peters, Florian, Lokau, Juliane, Scharfenberg, Franka, Werny, Ludwig, Linder, Stefan, Garbers, Christoph, Rose-John, Stefan, Becker-Pauly, Christoph
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
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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.
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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
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