MAPKAP kinase 2 is essential for LPS-induced TNF-α biosynthesis
Abstract
MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survive LPS-induced endotoxic shock. This is due to a reduction of approximately 90% in the production of tumor necrosis factor-alpha (TNF-alpha) and not to a change in signalling from the TNF receptor. The level and stability of TNF-alpha mRNA is not reduced and TNF-alpha secretion is not affected. We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-alpha at a post-transcriptional level.
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Suppression of IL-1β and related proinflammatory cytokine secretion is inhibited in MK2-/- mice, which are otherwise induced by MK2-mediated transcription.
“This suggests that suppression of IL-1β and related proinflammatory cytokine secretion is inhibited in MK2–/– mice, which are otherwise induced by MK2-mediated transcription [67].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [67]
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- Authors
- Kotlyarov, A., Neininger, A., Schubert, C., Eckert, R., Birchmeier, C., Volk, H.-D., & Gaestel, M.
- Affiliations
- Martin Luther University Halle-Wittenberg (DE)
- Humboldt-Universität zu Berlin (DE)
- Max Delbrück Center (DE)
- Corresponding author
- Gaestel, Matthias
- Venue
- Nature Cell Biology
- Published
- 1999-05-15
- Volume
- 1
- Issue
- 2
- Pages
- 94-97
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2127551467
- Cited by
- 763
- References
- 0
- Citations by year
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- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- MAPKAPK2, p38 MAPK, lipopolysaccharide, endotoxic shock, stress tolerance, post-transcriptional regulation, TNF receptor signaling, inflammation
- MeSH terms
- MAP-Kinase-Activated Kinase 2, Animals, Gene Expression Regulation, Inflammation, Lipopolysaccharides, Mice, Inbred Strains, Phosphorylation, RNA, Messenger, Salmonella typhi, Spleen, Transcription, Genetic, Tumor Necrosis Factor-alpha, Restriction Mapping, Cytokines, Mutagenesis, Protein Serine-Threonine Kinases, Mice, Knockout, Mitogen-Activated Protein Kinases, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Mice
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