Death Receptor
Introduction
The tumor necrosis factor receptor family, which includes TNF-RI, TNF-R2, Fas, DR3, DR4, DR5, and DR6, plays an important role in the regulation of apoptosis in various physiological systems. The receptors are activated by a family of cytokines that include TNF, FasL, TWEAK, and TRAIL. They are characterized by a highly conserved extracellular region containing cysteine-rich repeats and a conserved intracellular region of about 80 amino acids termed the death domain (DD). The DD is important for transducing the death signal by recruiting other DD containing adaptor proteins (FADD, TRADD, RIP) to the death-inducing signaling complex (DISC) resulting in activation of caspases.
The two receptors for TNF-α, TNF-R1 (55 kDa) and TNF-R2 (75 kDa) can mediate distinct cellular responses. In most cases cytotoxicity elicited by TNF has been reported to act through TNF-R1. DR3/WSL-1/Apo-3/TRAMP/LARD is a TNFR family member containing the characteristic extracellular cysteine-repeats, transmembrane region, and an intracellular DD. DR3 is activated by its ligand Apo-3L/TWEAK to induce apoptosis and activation of NF-κB. Like TNF-R1, DR3 binds to the DD adaptor protein TRADD, which can then associate with other DD proteins like FADD and RIP as well as members of the TRAF family.
Tissue expression of DR3 is very restricted, primarily seen on the surface of activated thymocytes and lymphocytes and plays an important role in thymocyte negative selection. Studies have also indicated an association with DR3 and rheumatoid arthritis. DR4 (TRAIL-RI, TNFRSF10A) and DR5 (TRAIL-R2, TNFRSF10B) are receptors for the cytokine TRAIL. Both receptors contain death domains that recruit DISC complexes triggering caspase activation and apoptosis.
DR6, also known as TNFRSF21, is a TNFR family member able to induce apoptosis as well as activation of NF-κB and JNK. DR6 appears to play a critical role in the activation and differentiation of T and B lymphocytes. In the nervous system, β-amyloid precursor protein (APP) activates DR6 to trigger neuronal degeneration.

Signal pathways related to autophagic cell death
Product Information
| Catalog# | Product Name | Application | Reactivity |
|---|---|---|---|
| AMRe21515 | Fas Rabbit Monoclonal antibody | WB,IHC,IF,IP,ELISA | Human |
| AMM82845 | TNFRSF1A Mouse Monoclonal Antibody | ICC,FC,ELISA | Human |
| AMRe19083 | TNF Receptor II (19A16) Rabbit Monoclonal Antibody | WB,IHC-P,ICC/IF,FC,IP,IF-P | Human,Mouse,Rat |
| AMRe10151 | DR5 (3Q11) Rabbit Monoclonal Antibody | WB,IHC-P,IP,IF-P | Human |
| AMRe01898 | DcR2 Rabbit Monoclonal Antibody | WB,IHC-P | Human |
| AMM82087 | TNFRSF6B Mouse Monoclonal Antibody | FC,ELISA | Human |
| AMRe10792 | FADD (16T14) Rabbit Monoclonal Antibody | WB,IHC-P,ICC/IF,FC,IP,IF-P | Human |
| AMRe19179 | TRADD (1A3) Rabbit Monoclonal Antibody | WB,IHC-P,ICC/IF,FC | Human |
| AMRe21588 | RIP Rabbit Monoclonal antibody | WB,IHC,IF,IP,ELISA | Human |
| APS0631 | HRP-conjugated Polyclonal Goat Anti-Mouse IgG(H+L) Secondary Antibody | ELISA, WB, Dot blot | Mouse |
| APS0635 | HRP-conjugated Polyclonal Goat Anti-Rabbit IgG(H+L) Secondary Antibody | Rabbit | ELISA, WB, Dot blot |
| AMre80004 | GAPDH (12R9) Rabbit Monoclonal Antibody | Human,Mouse,Rat,Rabbit,Dog,Monkey | WB,ELISA |
References
- Nagata S. Apoptosis by death factor. Cell. 1997 Feb 7;88(3):355-65. [PMID: 9039262].
- Thorburn A. Death receptor-induced cell killing. Cell Signal. 2004 Feb;16(2):139-44. [PMID: 14636884].
- Marsters SA, Sheridan JP, Pitti RM, Huang A, et,al. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol. 1997 Dec 1;7(12):1003-6. [PMID: 9382840].
- Pitti RM, Marsters SA, Lawrence DA, et,al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998 Dec 17;396(6712):699-703. doi: 10.1038/25387. PMID: 9872321.
- Stanger BZ, Leder P, Lee TH, Kim E, Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell. 1995 May 19;81(4):513-23. [PMID: 7538908].
- Ting AT, Pimentel-Muiños FX, Seed B. RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis. EMBO J. 1996 Nov 15;15(22):6189-96. [PMID: 8947041].
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