NFAT INTERACTIONS WITH THE VASOACTIVE-INTESTINAL-PEPTIDE CYTOKINE RESPONSE ELEMENT

The vasoactive intestinal peptide cytokine response element (VIP CyRE) is responsible for mediating the transcriptional induction of the VIP gene to the neuropoietic cytokines leukemia inhibitory factor (LIF) a nd ciliary neurotrophic factor (CNTF), In investigating the sequence a nd function of the CyRE, we found a region of DNA with homology to the distal NFAT site in the IL-2 promoter, In this paper we characterize this sequence and show that the VIP NFAT site recognizes T cell NFAT w ith similar affinity to the previously characterized IL-2 NFAT site. H owever, despite its location in the middle of the CyRE, we find no CNT F/LIF induced binding to it, Instead we show that in NBFL neuroblastom a cells, the calcium ionophore A23187 induces a protein to bind to the VIP NFAT site, This A23187-mediated induction of nuclear protein bind ing to an NFAT oligonucleotide is dependent on extracellular calcium b ut not dependent on de novo protein synthesis, Thus, this protein has the characteristics of an NFAT-like protein and is recognized by an NF AT3-specific antiserum suggesting that it is indeed an NFAT protein, T he location of the NFAT site in the VIP CyRE suggests that this may be one mechanism through which different signaling pathways engage in cr oss talk to alter VIP gene transcription. (C) 1998 Wiley-Liss, Inc.