PMID- 10094049
OWN - NLM
STAT- MEDLINE
DCOM- 19990407
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6724
DP  - 1999 Mar 18
TI  - The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade
      in the IL-1 signalling pathway.
PG  - 252-6
AB  - Interleukin-1 (IL-1) is a proinflammatory cytokine that has several effects in
      the inflammation process. When it binds to its cell-surface receptor, IL-1
      initiates a signalling cascade that leads to activation of the transcription
      factor NF-kappaB and is relayed through the protein TRAF6 and a succession of
      kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases
      (IKKs). However, the molecular mechanism by which NIK is activated is not
      understood. Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the
      IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1
      signalling. Stimulation of TAK1 causes activation of NF-kappaB, which is blocked 
      by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents
      activation of NF-kappaB that is mediated by IL-1 but not by NIK. Activated TAK1
      phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate
      that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.
FAU - Ninomiya-Tsuji, J
AU  - Ninomiya-Tsuji J
AD  - Department of Molecular Biology, Graduate School of Science, Nagoya University,
      and CREST, Japan Science and Technology Corporation.
FAU - Kishimoto, K
AU  - Kishimoto K
FAU - Hiyama, A
AU  - Hiyama A
FAU - Inoue, J
AU  - Inoue J
FAU - Cao, Z
AU  - Cao Z
FAU - Matsumoto, K
AU  - Matsumoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Interleukin-1)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
SB  - IM
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Enzyme Activation
MH  - I-kappa B Kinase
MH  - Interleukin-1/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *MAP Kinase Kinase Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Multienzyme Complexes/metabolism
MH  - Mutagenesis
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proteins/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Serine/metabolism
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 6
MH  - Threonine/metabolism
MH  - Transfection
EDAT- 1999/03/27 03:11
MHDA- 2001/03/23 10:01
CRDT- 1999/03/27 03:11
PHST- 1999/03/27 03:11 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/27 03:11 [entrez]
AID - 10.1038/18465 [doi]
PST - ppublish
SO  - Nature. 1999 Mar 18;398(6724):252-6. doi: 10.1038/18465.