MAPKAP kinase 2 is essential for LPS-induced TNF-α biosynthesis
A Kotlyarov, A Neininger, C Schubert, R Eckert… - Nature cell …, 1999 - nature.com
Nature cell biology, 1999•nature.com
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∼ 90% in the production of tumor necrosis factor-α (TNF-α) and not to a change
in signalling from the TNF receptor. The level and stability of TNF-α mRNA is not reduced …
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-α (TNF-α) and not to a change
in signalling from the TNF receptor. The level and stability of TNF-α mRNA is not reduced …
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∼ 90% in the production of tumor necrosis factor-α (TNF-α) and not to a change in signalling from the TNF receptor. The level and stability of TNF-α mRNA is not reduced and TNF-α secretion is not affected. We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-α at a post-transcriptional level.
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