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c‐ jun N‐terminal kinase is involved in AUUUA‐mediated interleukin‐3 mRNA turnover in mast cells
Author(s) -
Ming XiuFen,
Kaiser Mirjam,
Moroni Christoph
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.20.6039
Subject(s) - ionomycin , biology , wortmannin , messenger rna , transfection , microbiology and biotechnology , signal transduction , kinase , cell culture , pi3k/akt/mtor pathway , biochemistry , gene , genetics , intracellular
Whereas signalling pathways involved in transcriptional control have been studied extensively, the pathways regulating mRNA turnover remain poorly understood. We are interested in the role of mRNA stability in cell activation and oncogenesis using PB‐3c mast cells as a model system. In these cells the short‐lived interleukin‐3 (IL‐3) mRNA is stabilized by ionomycin treatment and following oncogenesis. To identify the signalling pathways involved in these mechanisms, we analysed the effect of different kinase inhibitors. SB202190 and wortmannin were shown to antagonize ionomycin‐induced IL‐3 mRNA stabilization in PB‐3c cells in the presence of actinomycin D, and this effect coincided with their ability to inhibit c‐ jun N‐terminal kinase (JNK) activation by ionomycin. Moreover, transfection of activated MEKK1 amplified ionomycin‐induced IL‐3 mRNA expression at the post‐transcriptional level, and a dominant‐negative mutant of JNK counteracted mRNA stabilization by ionomycin. Taken together, these data indicate that JNK is involved in the regulation of IL‐3 mRNA turnover in mast cells. In addition, transfection experiments revealed that the cis‐ acting AU‐rich element in the 3′ untranslated region of IL‐3 mRNA is necessary and sufficient to confer JNK‐dependent mRNA stabilization in response to cell activation.