NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase - PubMed (original) (raw)
. 1999 Sep 2;401(6748):82-5.
doi: 10.1038/43466.
Affiliations
- PMID: 10485710
- DOI: 10.1038/43466
NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase
O N Ozes et al. Nature. 1999.
Abstract
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.
Comment in
- Akt is more than just a Bad kinase.
Khwaja A. Khwaja A. Nature. 1999 Sep 2;401(6748):33-4. doi: 10.1038/43354. Nature. 1999. PMID: 10485701 No abstract available. - Kinase regulation in inflammatory response.
Delhase M, Li N, Karin M. Delhase M, et al. Nature. 2000 Jul 27;406(6794):367-8. doi: 10.1038/35019154. Nature. 2000. PMID: 10935625 No abstract available.
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