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

被引:678
作者
Kotlyarov, A
Neininger, A
Schubert, C
Eckert, R
Birchmeier, C
Volk, HD
Gaestel, M
机构
[1] Univ Halle Wittenberg, Innovat Kolleg Zellspezialisierung, D-06120 Halle, Germany
[2] Humboldt Univ, Inst Med Immunol, D-10098 Berlin, Germany
[3] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany
关键词
D O I
10.1038/10061
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 -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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收藏
页码:94 / 97
页数:4
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