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Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation

Nature volume 386, pages 296–299 (1997)Cite this article

Abstract

For cells of the innate immune system to mount a host defence response to infection, they must recognize products of microbial pathogens such as lipopolysaccharide (LPS), the endotoxin secreted by Gram-negative bacteria1. These cellular responses require intracellular signalling pathways, such as the four MAP kinase (MAPK) pathways2–6. In mammalian cells the MAPK p38 is thought to play an important role in the regulation of cellular responses during infection through its effects on the expression of proinflammatory molecules7–9. One means of understanding the role of p38 in these responses is to identify proteins with functions regulated by p38-catalysed phosphorylation. Here we demonstrate a link between the p38 pathway and a member of the myocyte-enhancer factor 2 (MEF2) group of transcription factors. We found that in monocytic cells, LPS increases the transactivation activity of MEF2C10–12 through p38-catalysed phosphorylation. One consequence of MEF2C activation is increased c-jun gene transcription. Our results show that p38 may influence host defence and inflammation by maintaining the balance of c-Jun protein consumed during infection.

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Authors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    J. Han, Y. Jiang, Z. Li, V. V. Kravchenko & R. J. Ulevitch

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  1. J. Han
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  2. Y. Jiang
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  3. Z. Li
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  4. V. V. Kravchenko
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  5. R. J. Ulevitch
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Han, J., Jiang, Y., Li, Z. et al. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 386, 296–299 (1997). https://doi.org/10.1038/386296a0

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