Editor-in-Chief: Brüne, Bernhard
Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred
IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162
CiteScore 2018: 3.09
SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820
The MKK6/p38 Mitogen-Activated Protein Kinase Pathway Is Capable of Inducing SOCS3 Gene Expression and Inhibits IL-6-Induced Transcription
In this study we show that activation of p38MAPKby IL-6 acts as an inhibitory signal on IL-6-mediated activation of STAT and the α2-macroglobulin promoter. We analyzed the role of MKK6/p38MAPKfor IL-6 signal transduction and transcriptional activation of the suppressor of cytokine signaling (SOCS) 3 promoter. Pretreatment of cells with the p38MAPKspecific inhibitor SB202190 downregulates the induction of SOCS3-mRNA expression by IL-6. Accordingly, overexpression of a constitutively active MKK6 in HepG2 cells enhanced basal activity or IL-6-induced transcriptional activation of a SOCS3 promoter reporter construct, whereas overexpression of a dominant negative mutant of MKK6 downregulated the IL-6-mediated activation of the SOCS3 promoter. These data indicate that p38MAPKactivation is crucial for IL-6-induced SOCS3 expression and downregulation of IL-6-mediated gene induction.
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