Cyclic AMP and calcium regulate at a transcriptional level the expression of the CD7 leukocyte differentiation antigen.
CD7 is a 40-kDa cell surface glycoprotein expressed on T-cell precursors before their entry into the thymus during fetal development and whose functional role remains uncertain. T-cell activation has been shown to increase the expression of this surface molecule. In this report we describe the intracellular signals and the mechanisms involved in the regulation of CD7 antigen expression on human T lymphocytes. The elevation of intracellular calcium by using the A23187 ionophore increased the cell surface expression of CD7, whereas protein kinase C activation caused its down-regulation. Interestingly, the increase of intracellular cAMP with Bt2cAMP stimulated CD7 expression as well. Upregulation of CD7 on the cell surface following either Bt2cAMP or calcium ionophore stimulation of T lymphocytes correlated with a raise of the steady-state levels of CD7-specific mRNA, without de novo protein synthesis requirements. No differences between the half-life of basal CD7 mRNA and that induced by either Bt2cAMP or calcium ionophore were detected. Run-on experiments showed that both stimuli enhanced the transcriptional rate of the CD7 gene. Our results provide the evidence for a positive regulatory effect mediated by cAMP on the expression of a leucocyte differentiation antigen.
Rincón
M
M
Sección de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
Tugores
A
A
López-Botet
M
M
D015703:Antigens, CD / Q000235:genetics*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D000001:Calcimycin; D012313:RNA; D003994:Bucladesine; D003513:Cycloheximide; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium