- search hit 1 of 1
Receptor Oligomerization and Its Relevance for Signaling by Receptors of the Tumor Necrosis Factor Receptor Superfamily
Please always quote using this URN: urn:nbn:de:bvb:20-opus-227180
- With the exception of a few signaling incompetent decoy receptors, the receptors of the tumor necrosis factor receptor superfamily (TNFRSF) are signaling competent and engage in signaling pathways resulting in inflammation, proliferation, differentiation, and cell migration and also in cell death induction. TNFRSF receptors (TNFRs) become activated by ligands of the TNF superfamily (TNFSF). TNFSF ligands (TNFLs) occur as trimeric type II transmembrane proteins but often also as soluble ligand trimers released from the membrane-bound form byWith the exception of a few signaling incompetent decoy receptors, the receptors of the tumor necrosis factor receptor superfamily (TNFRSF) are signaling competent and engage in signaling pathways resulting in inflammation, proliferation, differentiation, and cell migration and also in cell death induction. TNFRSF receptors (TNFRs) become activated by ligands of the TNF superfamily (TNFSF). TNFSF ligands (TNFLs) occur as trimeric type II transmembrane proteins but often also as soluble ligand trimers released from the membrane-bound form by proteolysis. The signaling competent TNFRs are efficiently activated by the membrane-bound TNFLs. The latter recruit three TNFR molecules, but there is growing evidence that this is not sufficient to trigger all aspects of TNFR signaling; rather, the formed trimeric TNFL–TNFR complexes have to cluster secondarily in the cell-to-cell contact zone for full TNFR activation. With respect to their response to soluble ligand trimers, the signaling competent TNFRs can be subdivided into two groups. TNFRs of one group, designated as category I TNFRs, are robustly activated by soluble ligand trimers. The receptors of a second group (category II TNFRs), however, failed to become properly activated by soluble ligand trimers despite high affinity binding. The limited responsiveness of category II TNFRs to soluble TNFLs can be overcome by physical linkage of two or more soluble ligand trimers or, alternatively, by anchoring the soluble ligand molecules to the cell surface or extracellular matrix. This suggests that category II TNFRs have a limited ability to promote clustering of trimeric TNFL–TNFR complexes outside the context of cell–cell contacts. In this review, we will focus on three aspects on the relevance of receptor oligomerization for TNFR signaling: (i) the structural factors which promote clustering of free and liganded TNFRs, (ii) the signaling pathway specificity of the receptor oligomerization requirement, and (iii) the consequences for the design and development of TNFR agonists.…
Author: | Kirstin Kucka, Harald Wajant |
---|---|
URN: | urn:nbn:de:bvb:20-opus-227180 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) |
Language: | English |
Parent Title (English): | Frontiers in Cell and Developmental Biology |
ISSN: | 2296-634X |
Year of Completion: | 2021 |
Volume: | 8 |
Article Number: | 615141 |
Source: | Frontiers in Cell and Developmental Biology 2021, 8:615141. doi: 10.3389/fcell.2020.615141 |
DOI: | https://doi.org/10.3389/fcell.2020.615141 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | NFκB; TNF ligand superfamily; TNF receptor (TNFR) family; cell death; receptor cluster |
Release Date: | 2021/03/16 |
Date of first Publication: | 2021/02/11 |
EU-Project number / Contract (GA) number: | 813871 |
OpenAIRE: | OpenAIRE |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |