Gene interactions and pathways from curated databases and text-mining
Nature 1999, PMID: 10485710

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

Ozes, O N; Mayo, L D; Gustin, J A; Pfeffer, S R; Pfeffer, L M; Donner, D B

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.

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Text Mining Data

serine-threonine kinase → NF-kappaB: " NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase "

IKB-kinase (IKK) → NF-kappaB: " 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 "

tumour necrosis factor (TNF) → serine-threonine kinase: " Here we show that the Akt serine-threonine kinase is involved in the activation of NF-kappaB by tumour necrosis factor (TNF) "

tumour necrosis factor (TNF) → NF-kappaB: " Here we show that the Akt serine-threonine kinase is involved in the activation of NF-kappaB by tumour necrosis factor (TNF) "

NF-kappaB → serine-threonine kinase: " Here we show that the Akt serine-threonine kinase is involved in the activation of NF-kappaB by tumour necrosis factor (TNF) "

Akt → TNF: " TNF activates phosphatidylinositol-3-OH kinase ( PI(3)K ) and its downstream target Akt ( protein kinase B ) "

NF-kappaB ⊣ Akt: " Wortmannin ( a PI(3)K inhibitor ), dominant negative PI(3)K or kinase-dead Akt inhibits TNF mediated NF-kappaB activation "

NF-kappaB ⊣ PI(3)K: " Wortmannin ( a PI(3)K inhibitor ), dominant negative PI(3)K or kinase-dead Akt inhibits TNF mediated NF-kappaB activation "

PI(3)K ⊣ Akt: " Wortmannin ( a PI(3)K inhibitor ), dominant negative PI(3)K or kinase-dead Akt inhibits TNF mediated NF-kappaB activation "

NF-kappaB → TNF: " Wortmannin ( a PI(3)K inhibitor ), dominant negative PI(3)K or kinase-dead Akt inhibits TNF mediated NF-kappaB activation "

NF-kappaB → Akt: " Constitutively active Akt induces NF-kappaB activity and this effect is blocked by dominant negative NIK "

NF-kappaB ⊣ Akt: " Conversely, NIK activates NF-kappaB and this is blocked by kinase-dead Akt "

TNF → Akt: " Thus, both Akt and NIK are necessary for TNF activation of NF-kappaB "

TNF → NF-kappaB: " Thus, both Akt and NIK are necessary for TNF activation of NF-kappaB "

NF-kappaB → Akt: " Thus, both Akt and NIK are necessary for TNF activation of NF-kappaB "

IKKalpha → Akt: " Akt mediates IKKalpha phosphorylation at threonine 23 "

TNF → NF-kappaB: " Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappaB "

Akt → NF-kappaB: " Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappaB "

Manually curated Databases

In total, 1 gene pairs are associated to this article in curated databases