PMID- 10485710
OWN - NLM
STAT- MEDLINE
DCOM- 19990927
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6748
DP  - 1999 Sep 2
TI  - NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine 
      kinase.
PG  - 82-5
AB  - Activation of the nuclear transcription factor NF-kappaB by inflammatory
      cytokines requires the successive action of NF-kappaB-inducing kinase (NIK) and
      an IKB-kinase (IKK) complex composed of IKKalpha and IKKbeta. Here we show that
      the Akt serine-threonine kinase is involved in the activation of NF-kappaB by
      tumour necrosis factor (TNF). TNF activates phosphatidylinositol-3-OH kinase
      (PI(3)K) and its downstream target Akt (protein kinase B). Wortmannin (a PI(3)K
      inhibitor), dominant-negative PI(3)K or kinase-dead Akt inhibits TNF-mediated
      NF-kappaB activation. Constitutively active Akt induces NF-kappaB activity and
      this effect is blocked by dominant-negative NIK. Conversely, NIK activates
      NF-kappaB and this is blocked by kinase-dead Akt. Thus, both Akt and NIK are
      necessary for TNF activation of NF-kappaB. Akt mediates IKKalpha phosphorylation 
      at threonine 23. Mutation of this amino acid blocks phosphorylation by Akt or TNF
      and activation of NF-kappaB. These findings indicate that Akt is part of a
      signalling pathway that is necessary for inducing key immune and inflammatory
      responses.
FAU - Ozes, O N
AU  - Ozes ON
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      the Walther Oncology Center, Indianapolis 46202, USA.
FAU - Mayo, L D
AU  - Mayo LD
FAU - Gustin, J A
AU  - Gustin JA
FAU - Pfeffer, S R
AU  - Pfeffer SR
FAU - Pfeffer, L M
AU  - Pfeffer LM
FAU - Donner, D B
AU  - Donner DB
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, CD)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2ZD004190S (Threonine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
SB  - IM
CIN - Nature. 1999 Sep 2;401(6748):33-4. PMID: 10485701
CIN - Nature. 2000 Jul 27;406(6794):367-8. PMID: 10935625
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Cell Line
MH  - DNA/metabolism
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase
MH  - Mice
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Signal Transduction
MH  - Threonine/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1999/09/15 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/15 09:00
PHST- 1999/09/15 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/15 09:00 [entrez]
AID - 10.1038/43466 [doi]
PST - ppublish
SO  - Nature. 1999 Sep 2;401(6748):82-5. doi: 10.1038/43466.