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

MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase, By introducing a targeted mutatio n into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survi ve 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 i n signalling from the TNF receptor. The level and stability of TNF-alpha mR NA 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.