Open AccessDifferent Apoptotic Pathways Mediated by Fas and the Tumor‐Necrosis‐Factor Receptor
Author(s) -
Enari Masato,
Hug Hubert,
Hayakawa Makio,
Ito Fumiaki,
Nishimura Yoshifumi,
Nagata Shigekazu
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.t01-1-00533.x
Subject(s) - fas receptor , apoptosis , tumor necrosis factor alpha , cytotoxic t cell , fas ligand , receptor , biology , microbiology and biotechnology , signal transduction , programmed cell death , death domain , cancer research , chemistry , immunology , biochemistry , in vitro
Fas is a cell‐surface receptor that belongs to the tumor‐necrosis factor (TNF)/nerve growth factor receptor family. Fas can transduce an apoptotic signal through the death domain in the cytoplasmic region, which has similarity with the corresponding region of the TNF type‐I receptor. Here, we expressed human Fas in mouse L929 cells or its subline (C12), which express extremely low levels of cytosolic phospholipase A 2 (cPLA 2 ). L929 cells were sensitive to the cytotoxic activity of TNF, while C12 cells were resistant. Cross‐linking of human Fas with anti‐(human Fas antibody) Ig killed both L929 transformants and C12 transformants expressing human Fas. Various inhibitors of the arachidonate metabolism significantly inhibited the TNF‐induced cytotoxicity in L929 cells, but they did not have any effect on Fas‐mediated apoptosis. These results indicated that cPLA, is required for TNF‐induced apoptosis, whereas it is dispensable for Fas‐mediated apoptosis, and suggested that the TNF receptor and Fas use different signaling pathways for apoptosis.