• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase.

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.

Pubmed ID: 10485710


  • Ozes ON
  • Mayo LD
  • Gustin JA
  • Pfeffer SR
  • Pfeffer LM
  • Donner DB



Publication Data

September 2, 1999

Associated Grants


Mesh Terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Cell Line
  • DNA
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • Mice
  • Molecular Sequence Data
  • NF-kappa B
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction
  • Threonine
  • Tumor Necrosis Factor-alpha