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Downregulation of Fas ligand by shedding

Nature Medicine volume 4, pages 31–36 (1998)Cite this article

Abstract

Apoptosis-inducing Fas ligand (FasL) is a type II membrane protein, predominantly expressed in the activated T cells. FasL is cleaved by a putative metalloproteinase to produce a soluble form. Here, we blocked the shedding of human FasL by deleting its cleavage site. Although human Jurkat cells and mouse primary hepatocytes that express a low level of Fas were resistant to the soluble form of FasL, they were efficiently killed by membrane-bound FasL. Furthermore, soluble FasL inhibited cytotoxicity of the membrane-bound FasL. These results indicate that the membrane-bound form of FasL is the functional form and suggest that shedding of FasL is to prevent the killing of the healthy bystander cells by cytotoxic T cells.

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Authors and Affiliations

  1. Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565, Japan

    Masato Tanaka, Toshimitsu Itai, Masashi Adachi & Shigekazu Nagata

  2. Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565, Japan

    Masato Tanaka & Shigekazu Nagata

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  2. Toshimitsu Itai
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  3. Masashi Adachi
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  4. Shigekazu Nagata
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Tanaka, M., Itai, T., Adachi, M. et al. Downregulation of Fas ligand by shedding. Nat Med 4, 31–36 (1998). https://doi.org/10.1038/nm0198-031

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