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| Verfasst von: | Koch, Lydia [VerfasserIn]  |
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| | Kespohl, Birte [VerfasserIn] |
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| | Agthe, Maria [VerfasserIn] |
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| | Schumertl, Tim [VerfasserIn] |
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| | Düsterhöft, Stefan [VerfasserIn] |
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| | Lemberg, Marius [VerfasserIn] |
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| | Lokau, Juliane [VerfasserIn] |
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| | Garbers, Christoph [VerfasserIn] |
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| Titel: | Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling |
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| Verf.angabe: | Lydia Koch, Birte Kespohl, Maria Agthe, Tim Schumertl, Stefan Düsterhöft, Marius K. Lemberg, Juliane Lokau, Christoph Garbers |
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| E-Jahr: | 2021 |
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| Jahr: | 10 February 2021 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 28.04.2021 |
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| Titel Quelle: | Enthalten in: Federation of American Societies for Experimental BiologyThe FASEB journal |
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| Ort Quelle: | Hoboken, NJ : Wiley, 1987 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 35(2021), 3, Artikel-ID e21380, Seite 1-15 |
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| ISSN Quelle: | 1530-6860 |
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| Abstract: | Interleukin-11 (IL-11) is a pleiotropic cytokine with both pro- and anti-inflammatory properties. It activates its target cells via binding to the membrane-bound IL-11 receptor (IL-11R), which then recruits a homodimer of the ubiquitously expressed, signal-transducing receptor gp130. Besides this classic signaling pathway, IL-11 can also bind to soluble forms of the IL-11R (sIL-11R), and IL-11/sIL-11R complexes activate cells via the induction of gp130 homodimerization (trans-signaling). We have previously reported that the metalloprotease ADAM10 cleaves the membrane-bound IL-11R and thereby generates sIL-11R. In this study, we identify the rhomboid intramembrane protease RHBDL2 as a so far unrecognized alternative sheddase that can efficiently trigger IL-11R secretion. We determine the cleavage site used by RHBDL2, which is located in the extracellular part of the receptor in close proximity to the plasma membrane, between Ala-370 and Ser-371. Furthermore, we identify critical amino acid residues within the transmembrane helix that are required for IL-11R proteolysis. We also show that ectopically expressed RHBDL2 is able to cleave the IL-11R within the early secretory pathway and not only at the plasma membrane, indicating that its subcellular localization plays a central role in controlling its activity. Moreover, RHBDL2-derived sIL-11R is biologically active and able to perform IL-11 trans-signaling. Finally, we show that the human mutation IL-11R-A370V does not impede IL-11 classic signaling, but prevents RHBDL2-mediated IL-11R cleavage. |
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| DOI: | doi:10.25673/96526 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Resolving-System: https://opendata.uni-halle.de//handle/1981185920/98483 |
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| | kostenfrei: Resolving-System: http://dx.doi.org/10.25673/96526 |
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| | kostenfrei: Resolving-System ; Verlag: https://doi.org/https://doi.org/10.1096/fj.202002087R |
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| | Volltext: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.202002087R |
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| | DOI: https://doi.org/10.25673/96526 |
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| | DOI: https://doi.org/10.1096/fj.202002087R |
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| URN: | urn:nbn:de:gbv:ma9:1-1981185920-984837 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | cytokine |
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| | interleukin-11 |
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| | protease |
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| | RHBDL2 |
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| | rhomboid |
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| K10plus-PPN: | 1756021872 |
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| Verknüpfungen: | → Zeitschrift |
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Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling / Koch, Lydia [VerfasserIn]; 10 February 2021 (Online-Ressource)
