Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Calcineurin
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Calcium / physiology
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Calmodulin-Binding Proteins / physiology
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Cyclosporine / metabolism
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Cyclosporine / pharmacology*
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DNA-Binding Proteins / chemistry
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Enhancer Elements, Genetic / drug effects*
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Gene Expression Regulation / immunology
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Humans
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Ionomycin / metabolism
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Ionomycin / pharmacology*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Nuclear Proteins / chemistry
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Phosphoprotein Phosphatases / physiology
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Receptors, Antigen, T-Cell, gamma-delta / drug effects*
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Spleen / metabolism
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T-Lymphocytes / metabolism
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Transcription Factors / chemistry
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Transcription, Genetic / immunology
Substances
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Calmodulin-Binding Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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Receptors, Antigen, T-Cell, gamma-delta
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Transcription Factors
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Ionomycin
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Cyclosporine
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Calcineurin
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Phosphoprotein Phosphatases
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Calcium