Identification of an ionomycin/cyclosporin A-responsive element within the human T cell receptor gamma enhancer.
Activation through the Ca2+/calcineurin pathway is essential to the transcription of many cytokine genes. The conserved cis-acting sequence, GGAAAA, and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations. Here we report the identification and importance of the same sequence in a non-cytokine gene, the human T cell receptor gamma (TCRG) enhancer. Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the TCRG enhancer. Our studies provide an explanation for a previous observation that TCRG mRNA levels, but not mRNA levels for T cell receptor alpha and -beta, are increased by ionomycin treatment.
Hettmann
T
T
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Cohen
A
A
D001483:Base Sequence; D019703:Calcineurin; D002118:Calcium / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000737:chemistry; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015759:Ionomycin / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic / Q000276:immunology
D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors; D015759:Ionomycin; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D002118:Calcium