NP-ATc isoforms are differentially expressed and regulated in murine T andmast cells

NF of activated T cells (NF-AT) denotes a family of transcription factors t hat regulate the activation-dependent expression of many immunologically im portant proteins, At least four distinct genes encode the various family me mbers, and several isoforms of these have been identified as web, The overl apping expression patterns and similar in vitro binding and trans-activatio n 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- a nd 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 ide ntified correspond to two NF-ATc isoforms that differ only in their amino-t erminal sequence, Despite minimal discrepancies in the coding region, there are striking tissue- and cell type-specific differences in isoform express ion patterns. Detection of NF-ATc.alpha mRNA is strictly dependent on cell activation signals in both T and mast cell lines. In contrast, the beta iso form is expressed at very low constitutive levels in both cell types hut is only up-regulated in response to mast cell activation signals delivered th rough the Fc epsilon RI or via calcium ionophores, These results demonstrat e another level of regulation within the NF-AT family that can contribute t o cell type-specific gene expression.