PMID- 10559880
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20091119
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 1
IP  - 2
DP  - 1999 Jun
TI  - MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis.
PG  - 94-7
AB  - 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.
FAU - Kotlyarov, A
AU  - Kotlyarov A
AD  - Martin-Luther-University Halle-Wittenberg, Germany.
FAU - Neininger, A
AU  - Neininger A
FAU - Schubert, C
AU  - Schubert C
FAU - Eckert, R
AU  - Eckert R
FAU - Birchmeier, C
AU  - Birchmeier C
FAU - Volk, H D
AU  - Volk HD
FAU - Gaestel, M
AU  - Gaestel M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
CIN - Nat Cell Biol. 1999 Jun;1(2):E39-40. PMID: 10559893
MH  - Animals
MH  - Cytokines/biosynthesis/*genetics
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Inflammation/genetics/immunology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/deficiency/*genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Restriction Mapping
MH  - Salmonella typhi
MH  - Spleen/immunology
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*genetics
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/11/13 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/11/13 09:00
PHST- 1999/11/13 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/11/13 09:00 [entrez]
AID - 10.1038/10061 [doi]
PST - ppublish
SO  - Nat Cell Biol. 1999 Jun;1(2):94-7. doi: 10.1038/10061.