Death Receptor Antibody Sampler Kit II#29603,Cell Signaling Technology (CST),29603

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 (1,2). 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 (3,4). In most cases cytotoxicity elicited by TNF has been reported to act through TNF-R1 (5,6). DR3/WSL-1/Apo-3/TRAMP/LARD is a TNFR family member containing the characteristic extracellular cysteine-repeats, transmembrane region, and an intracellular DD (7-11). DR3 is activated by its ligand Apo-3L/TWEAK to induce apoptosis and activation of NF-κB (12,13). 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 (7,8). 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 (7,8,14). Studies have also indicated an association with DR3 and rheumatoid arthritis (15,16). 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 (17-20). DR6, also known as TNFRSF21, is a TNFR family member able to induce apoptosis as well as activation of NF-κB and JNK (21). DR6 appears to play a critical role in the activation and differentiation of T and B lymphocytes (22,23). In the nervous system, β-amyloid precursor protein (APP) activates DR6 to trigger neuronal degeneration (24).Nagata, S. (1997)Cell88, 355-65.Thorburn, A. (2004)Cell Signal16, 139-44.Tartaglia, L.A. et al. (1991)Proc Natl Acad Sci U S A88, 9292-6.Peschon, J.J. et al. (1998)J Immunol160, 943-52.Tartaglia, L.A. et al. (1993)Cell73, 213-6.Rothe, J. et al. (1993)Nature364, 798-802.Chinnaiyan, A.M. et al. (1996)Science274, 990-2.Kitson, J. et al. (1996)Nature384, 372-5.Marsters, S.A. et al. (1996)Curr Biol6, 1669-76.Bodmer, J.L. et al. (1997)Immunity6, 79-88.Screaton, G.R. et al. (1997)Proc Natl Acad Sci U S A94, 4615-9.Marsters, S.A. et al. (1998)Curr Biol8, 525-8.Kaptein, A. et al. (2000)FEBS Lett485, 135-41.Wang, E.C. et al. (2001)Mol Cell Biol21, 3451-61.Osawa, K. et al. (2004)Genes Immun5, 439-43.Borysenko, C.W. et al. (2005)Biochem Biophys Res Commun328, 794-9.Pan, G. et al. (1997)Science276, 111-3.Walczak, H. et al. (1997)EMBO J16, 5386-97.Chaudhary, P.M. et al. (1997)Immunity7, 821-30.Schneider, P. et al. (1997)Immunity7, 831-6.Pan, G. et al. (1998)FEBS Lett431, 351-6.Zhao, H. et al. (2001)J Exp Med194, 1441-8.Schmidt, C.S. et al. (2003)J Exp Med197, 51-62.Nikolaev, A. et al. (2009)Nature457, 981-9.