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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The TNF receptor superfamily (TNFRSF, provisional nomenclature) displays limited homology beyond an extracellular domain rich in cysteine residues and is activated by at least 18 different human homologues of TNF referred to as the TNF superfamily (TNFSF). Some homologues lacking transmembrane and cytoplasmic domains function as decoy receptors binding ligand without inducing cell signalling. Many of these receptors and ligands function as multimeric entities. Signalling through these receptors is complex and involves interaction with cytoplasmic adaptor proteins (such as TRADD and TRAF1). Several of these receptors contain cytoplasmic motifs known as ‘death domains’, which upon activation serve to recruit death domain- and death effector domain-containing proteins crucial for the initiation of an apoptotic response. Additional signalling pathways include the regulation of the nuclear factor κB or mitogen-activated protein kinase pathways. Pharmacological manipulation of these receptors is mainly enacted through chelating the endogenous agonists with humanised monoclonal antibodies (e.g. Infliximab or adalimumab) or recombinant fusion proteins of IgG and soluble receptors (e.g. etanercept). Some mutated forms of TNF ligands are capable of selecting for different receptor subtypes.
* Key recommended reading is highlighted with an asterisk
* Aggarwal BB. (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat. Rev. Immunol., 3 (9): 745-56. [PMID:12949498]
* Ashkenazi A. (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat. Rev. Cancer, 2 (6): 420-30. [PMID:12189384]
Huang EJ, Reichardt LF. (2001) Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci., 24: 677-736. [PMID:11520916]
* Mahmood Z, Shukla Y. (2010) Death receptors: targets for cancer therapy. Exp. Cell Res., 316 (6): 887-99. [PMID:20026107]
* Rickert RC, Jellusova J, Miletic AV. (2011) Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol. Rev., 244 (1): 115-33. [PMID:22017435]
* Tansey MG, Szymkowski DE. (2009) The TNF superfamily in 2009: new pathways, new indications, and new drugs. Drug Discov. Today, 14 (23-24): 1082-8. [PMID:19837186]
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2. Jeon YH, Lee JY, Kim S. (2012) Chemical modulators working at pharmacological interface of target proteins. Bioorg. Med. Chem., 20 (6): 1893-901. [PMID:22227462]
3. Song Y, Margolles-Clark E, Bayer A, Buchwald P. (2014) Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction. Br. J. Pharmacol., 171 (21): 4955-69. [PMID:24930776]
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Database page citation:
David MacEwan. Tumour necrosis factor (TNF) receptor family. Accessed on 27/08/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=334.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol. 172: 5979-6023.