Comparison of apoptosis signaling through T cell receptor, fas, and calcium ionophore.
The SUP-T13 cell line, a human T leukemia, is susceptible to apoptosis by various inducers, including anti-TCR mAb, calcium ionophores, and anti-fas mAb. Induction of apoptosis by these three agents was investigated, and several differences were found. All three agents induced DNA fragmentation with a similar time course, but the kinetics of cell death were different for the three agents. Anti-TCR mAb-induced apoptosis, but not A23187- or anti-fas-induced apoptosis, was rescued by anti-CD3 mAb treatment. In contrast, only anti-fas mAb-mediated apoptosis was rescued by PKC activators such as PMA. These differences suggest that each of these three agents mediate apoptosis by unique signaling pathways. Nevertheless, two variant subclones of SUP-T13 were found to be resistant to all three apoptosis-inducing agents, suggesting a point(s) of common regulation between the different pathways. To determine whether this regulation occurred through bcl-2, p53, or c-myc, their expression in the parental and variant cells was determined. The three clones expressed approximately equal amounts of these proteins, and their levels did not change significantly upon treatment with anti-TCR or anti-TCR plus anti-CD3 mAb. Thus, although the proximal signaling by various apoptosis inducers were quite different, a common mediator(s) (as yet unknown) may still regulate apoptosis induced by these multiple agents.
Department of Medicine/Oncology, Stanford University Medical Center, California 94305, USA.
H T
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Maecker
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Hedjbeli
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Alzona
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D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D015458:Leukemia, T-Cell; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007476:Ionophores; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011948:Receptors, Antigen, T-Cell; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium