Membrane lymphotoxin-α\(_2\)β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist
Please always quote using this URN: urn:nbn:de:bvb:20-opus-260077
- In the early 1990s, it has been described that LTα and LTβ form LTα\(_2\)β and LTαβ\(_2\) heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ\(_2\)–LTβR system has been intensively studied while the LTα\(_2\)β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα\(_2\)β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα\(_2\)β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrateIn the early 1990s, it has been described that LTα and LTβ form LTα\(_2\)β and LTαβ\(_2\) heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ\(_2\)–LTβR system has been intensively studied while the LTα\(_2\)β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα\(_2\)β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα\(_2\)β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα\(_2\)β (memLTα\(_2\)β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα\(_2\)β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.…
Author: | Kirstin Kucka, Isabell Lang, Tengyu Zhang, Daniela Siegmund, Juliane Medler, Harald Wajant |
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URN: | urn:nbn:de:bvb:20-opus-260077 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) |
Language: | English |
Parent Title (English): | Cell Death & Disease |
Year of Completion: | 2021 |
Volume: | 12 |
Issue: | 4 |
Pagenumber: | 360 |
Source: | Cell Death & Disease (2021) 12:4, 360. doi:10.1038/s41419-021-03633-8 |
DOI: | https://doi.org/10.1038/s41419-021-03633-8 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | cytokines; signal transduction |
Release Date: | 2022/03/26 |
EU-Project number / Contract (GA) number: | 813871 |
OpenAIRE: | OpenAIRE |
Collections: | Open-Access-Publikationsfonds / Förderzeitraum 2021 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |