Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells.
Few known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA). We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression. Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA. The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133. In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA. This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts. This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it.
Mages
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Max-Planck-Society Research Unit for Immunology/Rheumatology, Erlangen University, Germany.
Stamminger
T
T
Rilke
O
O
Bravo
R
R
Kroczek
R A
RA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004357:Drug Synergism; D051776:Early Growth Response Protein 3; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016335:Zinc Fingers / Q000235:genetics
C079945:EGR3 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D051776:Early Growth Response Protein 3; D000001:Calcimycin; D016572:Cyclosporine; D004247:DNA; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate