NF-kappa B activation by tumour necrosis factor requires the Akt serine-threonine kinase.
Ozes, Osman Nidai; Mayo, Lindsey D.; Gustin, Jason A.; Pfeffer, Susan R.; Pfeffer, Lawrence M.; Donner, David B.
[Letter] Nature. 401(6748):82-85, September 2, 1999.

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Activation of the nuclear transcription factor NF-kappa B by inflammatory cytokines requires the successive action of NF-kappa B-inducing kinase (NIK) and an I kappa B-kinase (IKK) complex composed of IKK alpha and IKK beta [1-5]. Here we show that the Akt serine-threonine kinase [6] is involved in the activation of NF-kappa B 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-kappa B activation. Constitutively active Akt induces NF-kappa B activity and this effect is blocked by dominant-negative NIK. Conversely, NIK activates NF-kappa B and this is blocked by kinase-dead Akt. Thus, both Akt and NIK are necessary for TNF activation of NF-kappa B. Akt mediates IKK alpha phosphorylation at threonine 23. Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappa B. These findings indicate that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses.

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