DR4, also known as TRAILR1, was identified by searching an EST database with the death domain of TNFR1. DR4 contains two potential signal cleavage sites at Ala23/Ala24 and A110/Thr111.
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|Synonym:||CD261, TNFRSF10A, APO2, MGC9365, TRAILR-1, TRAILR1|
|Tag:||Mouse IgG2a Fc|
|Construction:||Human DR4 (A24-N239)-mouse IgG2a Fc|
|MW (calculated):||50,095 daltons|
|MW (SDS-PAGE):||55 Kd|
|Abs 0.1% (= 1 mg/ml):||1.031|
DR4, also known as TRAILR1, was identified by searching an EST database with the death domain of TNFR1. DR4 contains two potential signal cleavage sites at Ala23/Ala24 and A110/Thr111. It appears that the 2nd cleavage is used. If so, DR4 is very similar to DR5 for having a very long signal peptide.
DR4 contains the canonical structure of TNF receptors, including two extracellular cysteine-rich domain and the intracellular 70 amino-acid death domain. DR4 expresses in most human tissues including spleen, thymus and small intestine, and in a number of cell lines such as MCF7 breast carcinoma cells, K562 erythro-leukaemia cells as well as some activated T cells. Similar to TNFR1, Fas and DR3, overexpression of DR4 triggers apoptosis in MCF7 and 293 HEK (human embryonic kidney cells).
While it was originally reported that components mediating death signalling for DR4 are quite different from those used by TNFR1, DR3 and Fas, subsequent finding confirmed that DR4 does bind to FADD and TRADD and unlike the Fas, it does activate nuclear factor kappa B (NFκB). TRAIL is the only ligand for DR4. DR4-Fc does not bind to TNF-α or FasL, and is capable of blocking TRAIL-induced apoptosis.
Amino Acid Sequence.
1. Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM. (1997) The receptor for the cytotoxic ligand TRAIL. Science. 276:111-113.
2. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, et al. (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 3(6):673-682.
3. Hsu H, Xiong J, Goeddel DV. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495-504.
4. Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J. (1997) TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity. 7:831-836.