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PMID:10559880

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Citation

Kotlyarov, A, Neininger, A, Schubert, C, Eckert, R, Birchmeier, C, Volk, HD and Gaestel, M (1999) MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis. Nat. Cell Biol. 1:94-7

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.

Links

PubMed Online version:10.1038/10061

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MAPK2

involved_in

GO:0032496: response to lipopolysaccharide

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MAPK2

involved_in

GO:0032675: regulation of interleukin-6 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MAPK2

involved_in

GO:0032680: regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MAPK2

involved_in

GO:0006954: inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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