Activation of gene transcription by IL-4, IL-13 and IFN-gamma through a shared DNA binding motif.
Both interleukin-4 (IL-4) and interleukin-13 (IL-13) induce the transcription factor NF-IL4 (nuclear factor IL-4) which preexists in an inactive form and binds to an IL-4 responsive element (IL-4RE) in the promoter regions of IL-4/IL-13-dependent genes. UV-crosslinking and SDS gel electrophoresis indicate that NF-IL4 consists of at least two DNA-binding components of 50 kDa and 100-130 kDa. The IL-4 responsive element is also recognized by an interferon-gamma (IFN-gamma)-induced DNA binding protein for which a Mr of 50 kDa has been determined. A common DNA binding motif for different transcription factors might provide the basis for the frequently observed functional antagonism between IL-4/IL-13 and IFN-gamma. The activation of transcription factors by IL-4/IL-13 and IFN-gamma could be blocked by inhibitors of tyrosine kinases and ser/thr phosphatases but not by a PKC inhibitor, suggesting related signal transduction pathways for these cytokines.
Köhler
I
I
Institute for Immunology, Ludwig-Maximilians-University, München, Germany.
Alliger
P
P
Rieber
E P
EP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018793:Interleukin-13; C087516:NF-IL4 protein, human; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma