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Science 30 June 2000:
Vol. 288. no. 5475, pp. 2328 - 2329
DOI: 10.1126/science.288.5475.2328
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Perspectives

SIGNAL TRANSDUCTION:
FasL Binds Preassembled Fas

Pierre Golstein

The binding of a ligand to its receptor has always been viewed as the trigger for signal transduction to ensue. However, as Golstein explains in his Perspective, new findings (Chan et al. and Siegel et al.) suggest that the Fas receptor preassembles into trimers without the help of its ligand, and that this preassembly conditions ligand binding, and thus subsequent signal transduction of a death signal.

The author is at the Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France. E-mail: golstein{at}ciml.univ-mrs.fr

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A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome.
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Blood 108, 1306-1312
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Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis.
M. Miyaji, Z.-X. Jin, S. Yamaoka, R. Amakawa, S. Fukuhara, S. B. Sato, T. Kobayashi, N. Domae, T. Mimori, E. T. Bloom, et al. (2005)
J. Exp. Med. 202, 249-259
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Regulation of Lymphocyte Apoptosis by Interferon Regulatory Factor 4 (IRF-4).
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Tumor Necrosis Factor Receptor 1 Is an ATPase Regulated by Silencer of Death Domain.
K. Miki and E. M. Eddy (2002)
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Differential Secretion of Fas Ligand- or APO2 Ligand/TNF-Related Apoptosis-Inducing Ligand-Carrying Microvesicles During Activation-Induced Death of Human T Cells.
I. Monleon, M. J. Martinez-Lorenzo, L. Monteagudo, P. Lasierra, M. Taules, M. Iturralde, A. Pineiro, L. Larrad, M. A. Alava, J. Naval, et al. (2001)
J. Immunol. 167, 6736-6744
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Natural Ceramide Reverses Fas Resistance of Acid Sphingomyelinase-/- Hepatocytes.
F. Paris, H. Grassme, A. Cremesti, J. Zager, Y. Fong, A. Haimovitz-Friedman, Z. Fuks, E. Gulbins, and R. Kolesnick (2001)
J. Biol. Chem. 276, 8297-8305
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Ceramide Enables Fas to Cap and Kill.
A. Cremesti, F. Paris, H. Grassme, N. Holler, J. Tschopp, Z. Fuks, E. Gulbins, and R. Kolesnick (2001)
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