MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis - PubMed (original) (raw)

MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis

A Kotlyarov et al. Nat Cell Biol. 1999 Jun.

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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Comment in

• Emerging targets for anti-inflammatory therapy.
  Han J, Ulevitch RJ. Han J, et al. Nat Cell Biol. 1999 Jun;1(2):E39-40. doi: 10.1038/10032. Nat Cell Biol. 1999. PMID: 10559893 No abstract available.

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