Transcription of T cell antigen receptor genes is induced by protein kinase C activation.
The regulation of expression of the TCR-alpha and -beta genes was studied in the human T cell tumor line Jurkat. Treatment of the cells with PMA was shown to decrease the surface expression of the TCR-alpha/beta/CD3 complex. Subsequent to PMA-induced modulation of the TCR/CD3 complex, increases in the mRNA levels of both the TCR-alpha and -beta genes were observed reaching a maximum 12 h after stimulation. Other T cell activators were also examined for their ability to increase TCR-alpha and -beta mRNA expression. Only agents that activate protein kinase C were shown to induce expression of the TCR-alpha and -beta genes. The observed increases in TCR-alpha and -beta gene mRNA levels were not the result of a uniquely derived Jurkat subline. Similar inductions of TCR-alpha and -beta mRNA levels were observed in an independently maintained Jurkat cell line. In both cell lines, elevations of TCR gene expression was accompanied by a decline in the expression of the c-myc proto-oncogene. PMA induction of TCR-alpha and -beta mRNA was shown to occur in the presence of the protein synthesis inhibitor cycloheximide. The 1.6-kb TCR-alpha and the 1.0-kb D beta J beta C beta TCR-beta gene transcripts were fully induced in the presence of cycloheximide, whereas the 1.3-kb V beta D beta J beta C beta transcript was only partly induced in the presence of cycloheximide. Run-on transcription assays demonstrated that the increase in TCR-alpha and -beta mRNA levels could be entirely accounted for by increases in the transcription rate of both genes after PMA induction. Thus, in summary, protein kinase C stimulation leads to TCR-alpha/beta modulation in Jurkat cells and an increase in steady state TCR-alpha and -beta mRNA levels as a result of transcriptional activation of both genes.
Lindsten
T
T
Howard Hughes Medical Institute, Ann Arbor, MI 48109.
June
C H
CH
Thompson
C B
CB
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003513:Cycloheximide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate