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Brief Definitive Reports

From the Department of Biochemistry and the Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101

TRAIL-R3, a new member of the TRAIL receptor family, has been cloned and characterized. TRAIL-R3 encodes a 299 amino acid protein with 58 and 54% overall identity to TRAIL-R1 and -R2, respectively. Transient expression and quantitative binding studies show TRAIL-R3 to be a plasma membrane–bound protein capable of high affinity interaction with the TRAIL ligand. The TRAIL-R3 gene maps to human chromosome 8p22-21, clustered with the genes encoding two other TRAIL receptors. In contrast to TRAIL-R1 and -R2, this receptor shows restricted expression, with transcripts detectable only in peripheral blood lymphocytes and spleen. The structure of TRAIL-R3 is unique when compared to the other TRAIL receptors in that it lacks a cytoplasmic domain and appears to be glycosyl-phosphatidylinositol–linked. Moreover, unlike TRAIL-R1 and -R2, in a transient overexpression system TRAIL-R3 does not induce apoptosis.

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• Zhang, X. D., Franco, A., Myers, K., Gray, C., Nguyen, T., Hersey, P. (1999). Relation of TNF-related Apoptosis-inducing Ligand (TRAIL) Receptor and FLICE-inhibitory Protein Expression to TRAIL-induced Apoptosis of Melanoma. Cancer Res. 59: 2747-2753 [Abstract] [Full Text]  
• Wu, G. S., Burns, T. F., Zhan, Y., Alnemri, E. S., El-Deiry, W. S. (1999). Molecular Cloning and Functional Analysis of the Mouse Homologue of the KILLER/DR5 Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Death Receptor. Cancer Res. 59: 2770-2775 [Abstract] [Full Text]  
• Phillips, T. A., Ni, J., Pan, G., Ruben, S. M., Wei, Y.-F., Pace, J. L., Hunt, J. S. (1999). TRAIL (Apo-2L) and TRAIL Receptors in Human Placentas: Implications for Immune Privilege. J. Immunol. 162: 6053-6059 [Abstract] [Full Text]  
• Yu, K.-Y., Kwon, B., Ni, J., Zhai, Y., Ebner, R., Kwon, B. S. (1999). A Newly Identified Member of Tumor Necrosis Factor Receptor Superfamily (TR6) Suppresses LIGHT-mediated Apoptosis. J. Biol. Chem. 274: 13733-13736 [Abstract] [Full Text]  
• Griffith, T. S., Wiley, S. R., Kubin, M. Z., Sedger, L. M., Maliszewski, C. R., Fanger, N. A. (1999). Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor-related Cytokine, TRAIL. JEM 189: 1343-1354 [Abstract] [Full Text]  
• Kwon, B., Yu, K.-Y., Ni, J., Yu, G.-L., Jang, I.-K., Kim, Y.-J., Xing, L., Liu, D., Wang, S.-X., Kwon, B. S. (1999). Identification of a Novel Activation-inducible Protein of the Tumor Necrosis Factor Receptor Superfamily and Its Ligand. J. Biol. Chem. 274: 6056-6061 [Abstract] [Full Text]  
• Griffith, T. S., Rauch, C. T., Smolak, P. J., Waugh, J. Y., Boiani, N., Lynch, D. H., Smith, C. A., Goodwin, R. G., Kubin, M. Z. (1999). Functional Analysis of TRAIL Receptors Using Monoclonal Antibodies. J. Immunol. 162: 2597-2605 [Abstract] [Full Text]  
• Kayagaki, N., Yamaguchi, N., Nakayama, M., Kawasaki, A., Akiba, H., Okumura, K., Yagita, H. (1999). Involvement of TNF-Related Apoptosis-Inducing Ligand in Human CD4+ T Cell-Mediated Cytotoxicity. J. Immunol. 162: 2639-2647 [Abstract] [Full Text]  
• Keane, M. M., Ettenberg, S. A., Nau, M. M., Russell, E. K., Lipkowitz, S. (1999). Chemotherapy Augments TRAIL-induced Apoptosis in Breast Cell Lines. Cancer Res. 59: 734-741 [Abstract] [Full Text]  
• Zamai, L., Ahmad, M., Bennett, I. M., Azzoni, L., Alnemri, E. S., Perussia, B. (1998). Natural Killer (NK) Cell-mediated Cytotoxicity: Differential Use of TRAIL and Fas Ligand by Immature and Mature Primary Human NK Cells. JEM 188: 2375-2380 [Abstract] [Full Text]  
• Spielman, J., Lee, R. K., Podack, E. R. (1998). Perforin/Fas-Ligand Double Deficiency Is Associated with Macrophage Expansion and Severe Pancreatitis. J. Immunol. 161: 7063-7070 [Abstract] [Full Text]  
• Muhlenbeck, F., Haas, E., Schwenzer, R., Schubert, G., Grell, M., Smith, C., Scheurich, P., Wajant, H. (1998). TRAIL/Apo2L Activates c-Jun NH2-terminal Kinase (JNK) via Caspase-dependent and Caspase-independent Pathways. J. Biol. Chem. 273: 33091-33098 [Abstract] [Full Text]  
• Kothny-Wilkes, G., Kulms, D., Poppelmann, B., Luger, T. A., Kubin, M., Schwarz, T. (1998). Interleukin-1 Protects Transformed Keratinocytes from Tumor Necrosis Factor-related Apoptosis-inducing Ligand. J. Biol. Chem. 273: 29247-29253 [Abstract] [Full Text]  
• Harrop, J. A., McDonnell, P. C., Brigham-Burke, M., Lyn, S. D., Minton, J., Tan, K. B., Dede, K., Spampanato, J., Silverman, C., Hensley, P., DiPrinzio, R., Emery, J. G., Deen, K., Eichman, C., Chabot-Fletcher, M., Truneh, A., Young, P. R. (1998). Herpesvirus Entry Mediator Ligand (HVEM-L), a Novel Ligand for HVEM/TR2, Stimulates Proliferation of T Cells and Inhibits HT29 Cell Growth. J. Biol. Chem. 273: 27548-27556 [Abstract] [Full Text]  
• Craxton, A., Shu, G., Graves, J. D., Saklatvala, J., Krebs, E. G., Clark, E. A. (1998). p38 MAPK Is Required for CD40-Induced Gene Expression and Proliferation in B Lymphocytes. J. Immunol. 161: 3225-3236 [Abstract] [Full Text]  
• Griffith, T. S., Chin, W. A., Jackson, G. C., Lynch, D. H., Kubin, M. Z. (1998). Intracellular Regulation of TRAIL-Induced Apoptosis in Human Melanoma Cells. J. Immunol. 161: 2833-2840 [Abstract] [Full Text]  
• Thomas, W. D., Hersey, P. (1998). TNF-Related Apoptosis-Inducing Ligand (TRAIL) Induces Apoptosis in Fas Ligand-Resistant Melanoma Cells and Mediates CD4 T Cell Killing of Target Cells. J. Immunol. 161: 2195-2200 [Abstract] [Full Text]  
• Ashkenazi, A., Dixit, V. M. (1998). Death Receptors: Signaling and Modulation. Science 281: 1305-1308 [Abstract] [Full Text]  
• Harrop, J. A., Reddy, M., Dede, K., Brigham-Burke, M., Lyn, S., Tan, K. B., Silverman, C., Eichman, C., DiPrinzio, R., Spampanato, J., Porter, T., Holmes, S., Young, P. R., Truneh, A. (1998). Antibodies to TR2 (Herpesvirus Entry Mediator), a New Member of the TNF Receptor Superfamily, Block T Cell Proliferation, Expression of Activation Markers, and Production of Cytokines. J. Immunol. 161: 1786-1794 [Abstract] [Full Text]  
• Jeremias, I., Kupatt, C., Baumann, B., Herr, I., Wirth, T., Debatin, K.M. (1998). Inhibition of Nuclear Factor kappa B Activation Attenuates Apoptosis Resistance in Lymphoid Cells. Blood 91: 4624-4631 [Abstract] [Full Text]  

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