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NF-ATc Isoforms Are Differentially Expressed and Regulated in Murine T and Mast Cells^{1 ,2}

Melanie A. Sherman^*, Doris R. Powell^*, Deborah L. Weiss and Melissa A. Brown^3,*,

^* Department of Experimental Pathology, and Graduate Program in Immunology and Molecular Pathogenesis and Genetics and Molecular Biology, Emory University School of Medicine, Atlanta, GA 30322; and Department of Chemistry, Williams College, Williamstown, MA 02167

NF of activated T cells (NF-AT) denotes a family of transcription factors that regulate the activation-dependent expression of many immunologically important proteins. At least four distinct genes encode the various family members, and several isoforms of these have been identified as well. The overlapping expression patterns and similar in vitro binding and trans-activation activities on various promoter elements of NF-AT-regulated genes suggest some redundancy in the function of these proteins. However, the phenotypic analysis of NF-AT-deficient mice supports the idea that there are tissue- and gene-specific functions as well. In this study we have characterized the expression of NF-AT cDNAs in murine mast cells. The majority of clones identified correspond to two NF-ATc isoforms that differ only in their amino-terminal sequence. Despite minimal discrepancies in the coding region, there are striking tissue- and cell type-specific differences in isoform expression patterns. Detection of NF-ATc. mRNA is strictly dependent on cell activation signals in both T and mast cell lines. In contrast, the ß isoform is expressed at very low constitutive levels in both cell types but is only up-regulated in response to mast cell activation signals delivered through the FcRI or via calcium ionophores. These results demonstrate another level of regulation within the NF-AT family that can contribute to cell type-specific gene expression.

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