A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen.
The Fas antigen is a cell surface protein that can mediate apoptosis and that belongs to the tumor necrosis factor receptor family. Murine fibroblast L929 cells or T-cell lymphoma WR19L cells expressing the human Fas antigen were killed within 4-6 h by anti-human Fas antibody in a concentration-dependent manner. Human Fas antigen cDNAs with various mutations in the cytoplasmic region were constructed and expressed in L929 cells. A deletion of 15 amino acids from the C terminus of the Fas antigen enhanced the Fas antibody-induced killing activity, whereas a further deletion abolished its activity. This suggests the presence of an inhibitory as well as a signal-transducing domain in the cytoplasmic region of the Fas antigen. A 68-amino acid portion of the signal-transducing domain significantly conserved in the Fas antigen as well as in the type I tumor necrosis factor receptor was considered to be the novel protein domain required for apoptotic signal transduction.
Itoh
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N
Osaka Bioscience Institute, Japan.
Nagata
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S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007739:L Cells; D016399:Lymphoma, T-Cell; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor