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Science 288 (5475): 2351-2354

Copyright © 2000 by the American Association for the Advancement of Science

A Domain in TNF Receptors That Mediates Ligand-Independent Receptor Assembly and Signaling

Francis Ka-Ming Chan, Hyung J. Chun, Lixin Zheng, Richard M. Siegel, Kimmie L. Bui, * Michael J. Lenardo dagger

A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
*   Present address: George Washington University School of Medicine, Washington, DC 20037, USA.

dagger    To whom correspondence should be addressed. E-mail: Lenardo{at}nih.gov



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P. Schneider, D. Olson, A. Tardivel, B. Browning, A. Lugovskoy, D. Gong, M. Dobles, S. Hertig, K. Hofmann, H. Van Vlijmen, et al. (2003)
J. Biol. Chem. 278, 5444-5454
   Abstract »    Full Text »    PDF »
Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-I) in active lupus.
F Silvestris, D Grinello, M Tucci, P Cafforio, and F Dammacco (2003)
Lupus 12, 8-14
   Abstract »    PDF »
Lipopolysaccharide Rapidly Traffics to and from the Golgi Apparatus with the Toll-like Receptor 4-MD-2-CD14 Complex in a Process That Is Distinct from the Initiation of Signal Transduction.
E. Latz, A. Visintin, E. Lien, K. A. Fitzgerald, B. G. Monks, E. A. Kurt-Jones, D. T. Golenbock, and T. Espevik (2002)
J. Biol. Chem. 277, 47834-47843
   Abstract »    Full Text »    PDF »
LMP-1's Transmembrane Domains Encode Multiple Functions Required for LMP-1's Efficient Signaling.
A. Kaykas, K. Worringer, and B. Sugden (2002)
J. Virol. 76, 11551-11560
   Abstract »    Full Text »    PDF »
TRAIL/Apo-2 Ligand Induces Primary Plasma Cell Apoptosis.
J. Ursini-Siegel, W. Zhang, A. Altmeyer, E. N. Hatada, R. K. G. Do, H. Yagita, and S. Chen-Kiang (2002)
J. Immunol. 169, 5505-5513
   Abstract »    Full Text »    PDF »
Control of Receptor-induced Signaling Complex Formation by the Kinetics of Ligand/Receptor Interaction.
A. Krippner-Heidenreich, F. Tubing, S. Bryde, S. Willi, G. Zimmermann, and P. Scheurich (2002)
J. Biol. Chem. 277, 44155-44163
   Abstract »    Full Text »    PDF »
Etk/Bmx as a Tumor Necrosis Factor Receptor Type 2-Specific Kinase: Role in Endothelial Cell Migration and Angiogenesis.
S. Pan, P. An, R. Zhang, X. He, G. Yin, and W. Min (2002)
Mol. Cell. Biol. 22, 7512-7523
   Abstract »    Full Text »    PDF »
Structure-Based Analysis of the Herpes Simplex Virus Glycoprotein D Binding Site Present on Herpesvirus Entry Mediator HveA (HVEM).
S. A. Connolly, D. J. Landsburg, A. Carfi, D. C. Wiley, R. J. Eisenberg, and G. H. Cohen (2002)
J. Virol. 76, 10894-10904
   Abstract »    Full Text »    PDF »
BLyS and APRIL Form Biologically Active Heterotrimers That Are Expressed in Patients with Systemic Immune-Based Rheumatic Diseases.
V. Roschke, S. Sosnovtseva, C. D. Ward, J. S. Hong, R. Smith, V. Albert, W. Stohl, K. P. Baker, S. Ullrich, B. Nardelli, et al. (2002)
J. Immunol. 169, 4314-4321
   Abstract »    Full Text »    PDF »
Regulation of the Subcellular Localization of Tumor Necrosis Factor Receptor-associated Factor (TRAF)2 by TRAF1 Reveals Mechanisms of TRAF2 Signaling.
J. R. Arron, Y. Pewzner-Jung, M. C. Walsh, T. Kobayashi, and Y. Choi (2002)
J. Exp. Med. 196, 923-934
   Abstract »    Full Text »    PDF »
Rabies Virus Glycoprotein (RVG) Is a Trimeric Ligand for the N-terminal Cysteine-rich Domain of the Mammalian p75 Neurotrophin Receptor.
C. Langevin, H. Jaaro, S. Bressanelli, M. Fainzilber, and C. Tuffereau (2002)
J. Biol. Chem. 277, 37655-37662
   Abstract »    Full Text »    PDF »
Seeing the Light: Preassembly and Ligand-Induced Changes of the Interferon {gamma} Receptor Complex in Cells.
C. D. Krause, E. Mei, J. Xie, Y. Jia, M. A. Bopp, R. M. Hochstrasser, and S. Pestka (2002)
Mol. Cell. Proteomics 1, 805-815
   Abstract »    Full Text »    PDF »
CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes.
T. Becker, F.-U. Hartl, and F. Wieland (2002)
J. Cell Biol. 158, 1277-1285
   Abstract »    Full Text »    PDF »
Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics.
A. Berezov, J. Chen, Q. Liu, H.-T. Zhang, M. I. Greene, and R. Murali (2002)
J. Biol. Chem. 277, 28330-28339
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Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue.
J. F. Panus, C. A. Smith, C. A. Ray, T. D. Smith, D. D. Patel, and D. J. Pickup (2002)
PNAS 99, 8348-8353
   Abstract »    Full Text »    PDF »

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