P21(RAS) LINKS FC-EPSILON-RI TO NF-AT FAMILY MEMBER IN MAST-CELLS - THE AP3-LIKE FACTOR IN THIS CELL-TYPE IS AN NF-AT FAMILY MEMBER

Very recently, an AP3-like transcription factor regulating the chemoki ne gene MARC and an NF-AT family member regulating IL-5 were the first components of the transcription factor repertoire to be described as activated in mast cells after an allergic triggering. In this study, w e show that with respect to cross-competition in a gel shift analysis using an NF-AT consensus oligonucleotide binding site, the antigenicit y to a recently generated serum against T cell NF-AT, and the sensitiv ity to macrolide immunosuppressants, the AP3-like activity on the MARC promoter is indistinguishable from that described for NF-AT in T cell s. Additionally, we show that this factor functions on the MARC chemok ine promoter without the AP1 cofactor, a situation reminiscent of the function of NF-AT in Th2-type T cells. In all of these aspects, and st rengthened further by a gel shift competition analysis, the AP3-like t ranscription factor is identical to the NF-AT family member recently d escribed by an analogous set of experiments as regulating IL-5 in mast cells. Our finding that p21(ras), but probably not protein kinase C, is necessary to activate this factor after Fc epsilon RI triggering in dicates a situation in which a common transcription factor denominator in mast cells induces chemokine (MARC) and lymphokine (IL-5) gene exp ression in a manner closely similar to Th2-type T cells, which are ind uced along the ras/raf signal pathway.