p21ras 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 chemokine 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, we show that with respect to cross-competition in a gel shift analysis using an NF-AT consensus oligonucleotide binding site, the antigenicity to a recently generated serum against T cell NF-AT, and the sensitivity to macrolide immunosuppressants, the AP3-like activity on the MARC promoter is indistinguishable from that described for NF-AT in T cells. Additionally, we show that this factor functions on the MARC chemokine 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 strengthened further by a gel shift competition analysis, the AP3-like transcription factor is identical to the NF-AT family member recently described by an analogous set of experiments as regulating IL-5 in mast cells. Our finding that p21ras, but probably not protein kinase C, is necessary to activate this factor after Fc epsilon RI triggering indicates a situation in which a common transcription factor denominator in mast cells induces chemokine (MARC) and lymphokine (IL-5) gene expression in a manner closely similar to Th2-type T cells, which are induced along the ras/raf signal pathway.
Prieschl
E E
EE
Department of Immunodermatology, Sandoz Research Institute, Vienna, Austria.
Pendl
G G
GG
Harrer
N E
NE
Baumruker
T
T
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D015848:Interleukin-5; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017455:Receptors, IgE; D014157:Transcription Factors; D016283:Proto-Oncogene Proteins p21(ras)