Distinct mechanisms of c-myc and lymphokine gene expression in an antigen specific T cell clone.
Experiments were performed to examine the mechanisms regulating the expression of the c-myc gene and the IL-2 and interferon gamma (IFN-gamma) lymphokine genes in an antigen-specific murine T cell clone. IL-2 and the mitogenic lectin, concanavalin A (Con A), as well as the calcium ionophore ionomycin, in concert with phorbol ester, (PMA) enhanced c-myc gene transcription, but by distinct mechanisms as demonstrated by differential sensitivity to inhibition of protein synthesis and by transcriptional run-off assays using c-myc exon 1 and exon 2 probes. Induction of c-myc expression by IL-2, but not lectin or ionomycin plus phorbol ester, was inhibited in the presence of cycloheximide. IL-2 induced the transcription of both c-myc exons 1 and 2, whereas Con A primarily enhanced exon 1 to exon 2 transcriptional read-through. A direct relationship was observed between the level of early c-myc expression following IL-2 stimulation and the magnitude of the subsequent clonal proliferative response. Lymphokine gene expression was enhanced by Con A, but not by IL-2. Induction of the lymphokine genes in this T cell clone was under predominant post-transcriptional control and was sensitive to protein synthesis inhibition. Therefore, mitogenic lectins induce c-myc and lymphokine gene expression via different pathways.
Heckford
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SE
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892.
Gelmann
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EP
Matis
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D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells; D003208:Concanavalin A / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D005091:Exons; D015870:Gene Expression / Q000187:drug effects; D005796:Genes; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D015342:DNA Probes; D007376:Interleukin-2; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D003208:Concanavalin A; D007371:Interferon-gamma; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate