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

Nat Cell Biol. 1999 Jun;1(2):94-7. doi: 10.1038/10061.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Inflammation / genetics
  • Inflammation / immunology
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutagenesis
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Restriction Mapping
  • Salmonella typhi
  • Spleen / immunology
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases