DR4, Fc Chimera, Recombinant, Human (Tumor Necrosis Factor Receptor Superfamily Member 10A, Death Receptor 4, TNF-related Apoptosis-inducing Ligand Receptor 1, TRAIL Receptor 1, TRAIL-R1, CD261, TNFRSF10A, APO2, TRAILR1)

Human TRAIL R1 also called DR4 (death receptor 4), is a 50-57kD, 468aa type 1 transmembrane protein in the TNF R family, designated TNFRSF10A. Of the five receptors for TRAIL (also called APO2 ligand) in humans, TRAIL R1/DR4 and TRAIL R2/DR5 are apoptosis-inducing and share 59% aa identity within the cytoplasmic death domain aa365- 448 of human TRAIL R1. Rodents do not express TRAIL R1/DR4. Human decoy receptors TRAIL R3 and TRAIL R4 have non-functional death domains but share ~60% aa identity with TRAIL R1 within extracellular TNFR domains aa107-229 while the secreted TRAIL receptor osteoprotegerin shares only 18% aa identity with TRAIL R1. Trimeric TRAIL engagement of TRAIL R1 induces apoptosis by recruiting a cytosolic death-inducing signaling complex (DISC) that includes the adaptor FADD and caspases 8 and 10. TRAIL R1 translational modifications, such as O-glycosylation and palmitoylation, promote apoptosis by enhancing oligomerization and presence in lipid rafts, respectively. Recombinant human TRAIL R1 neutralizes the ability of TRAIL to induce apoptosis. TRAIL R1 protein is expressed mainly in damaged, infected and malignant cells and can be repressed by hedgehog proteins in oncogenic cells. TRAIL R1 is also expressed on hemopoietic cells and influences activities such as monocyte migration. On senescent neutrophils, CXCL12/SDF-1 engagement of CXCR4 induces expression of all TRAIL R. TRAIL functions in immune surveillance, inducing apoptosis in cancer cells but not normal cells. TRAIL R1 surface expression correlates more closely than that of TRAIL R2 with TRAIL induction of apoptosis on tumor cells such as melanoma and chronic lymphocytic and acute myeloid leukemias.\n\nSource:\nRecombinant corresponding to aa1-239 from human TRAIL R1 expressed in CHO cell line.\n\nMolecular Weight:\n~40.9kD\n\nBiological Activity:\nMeasured by its ability to inhibit TRAIL-mediated cytotoxicity using L-929 mouse fibrosarcoma cells treated with TRAIL. The ED50 for this effect is typically 0.25-1.25ng/ml in the presence of 6ng/ml of Recombinant Human TNFSF10.\n\nEndotoxin: ~1EU/1ug (LAL)\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 3 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

D9300-36A

Size

100ug

Form

Supplied as a lyophilized powder in PBS. BSA free. Reconstitute with sterile PBS to 0.1mg/ml.

Purity

~95% (SDS-PAGE)

References

1. Pan, G. et al. (1997) Science 276:111. 2. Zauli, G. and P. Secchiero (2006) Cytokine Growth Factor Rev. 17:245. 3. Yang, A. et al. (2010) Curr. Opin. Cell Biol. 22:837. 4. Rossin, A. et al. (2009) Biohem. J. 419:185. 5. Psahoulia, F.H. et al. (2007) Mol. Cancer Ther. 6:2591. 6. Ries, C.R. et al. (2010) Cell Death Dis. 1:e83. 7. Lum, J.J. et al. (2005) J. Immunol. 175:1232. 8. Kurita, S. et al. (2010) Oncogene 29:4848. 9. Wei, W. et al. (2010) Mol. Immunol. 47:2475.10. Sung, E