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Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin ß and MT1-MMP.
Sammel, Martin; Peters, Florian; Lokau, Juliane; Scharfenberg, Franka; Werny, Ludwig; Linder, Stefan; Garbers, Christoph; Rose-John, Stefan; Becker-Pauly, Christoph.
Afiliação
  • Sammel M; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
  • Peters F; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
  • Lokau J; Institute of Pathology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
  • Scharfenberg F; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
  • Werny L; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
  • Linder S; Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, 20246, Hamburg, Germany.
  • Garbers C; Institute of Pathology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
  • Rose-John S; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
  • Becker-Pauly C; Institute of Biochemistry, University of Kiel, Otto-Hahn-Platz 9, 24118 Kiel, Germany. cbeckerpauly@biochem.uni-kiel.de.
Int J Mol Sci ; 20(15)2019 Jul 26.
Article em En | MEDLINE | ID: mdl-31357561
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 ß, 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metaloendopeptidases / Proteínas ADAM / Metaloproteinase 14 da Matriz / Receptores de Interleucina-11 Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metaloendopeptidases / Proteínas ADAM / Metaloproteinase 14 da Matriz / Receptores de Interleucina-11 Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article