Segregation of APO-1/Fas antigen- and tumor necrosis factor receptor-mediated apoptosis.
The cytokine tumor necrosis factor (TNF) and the APO-1/Fas ligand represent typical inducers of apoptosis, i.e. programmed cell death. A limited sequence homology between the TNF receptor TR60 (p55) and the APO-1/Fas (CD95) antigen in their intracellular domains suggests overlapping signaling pathways. The TNF-sensitive cell line KYM-1, which expresses high numbers of both TNF receptors and the APO-1/Fas antigen, is highly sensitive towards triggering of apoptosis by each of the TNF receptors, but resistant to APO-1/Fas stimulation. The opposite response pattern was obtained using the B lymphoid line SKW 6.4, which also co-expresses all three cell surface molecules. Furthermore, no co-modulation of APO-1/Fas by down-regulation of cell surface expressed TR60 and/or TR80 receptors, and vice versa, was found. These data argue against a physical interaction of TNF receptors with APO-1/Fas and, in addition, demonstrate cell specific control of induction of apoptosis and usage of distinct signaling pathways by these receptor molecules.
Grell
M
M
Institute of Cell Biology and Immunology, University of Stuttgart, Germany.
Krammer
P H
PH
Scheurich
P
P
D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D015536:Down-Regulation; D006801:Humans; D066298:In Vitro Techniques; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000954:Antigens, Surface; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor