NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase

摘要: Activation of the nuclear transcription factor NF-kappaB by inflammatory cytokines requires successive action NF-kappaB-inducing kinase (NIK) and an IKB-kinase (IKK) complex composed IKKalpha IKKbeta. Here we show that Akt serine-threonine is involved in activation tumour necrosis (TNF). TNF activates phosphatidylinositol-3-OH (PI(3)K) its downstream target (protein B). Wortmannin (a PI(3)K inhibitor), dominant-negative or kinase-dead inhibits TNF-mediated activation. Constitutively active induces activity this effect blocked NIK. Conversely, NIK Akt. Thus, both are necessary for NF-kappaB. mediates phosphorylation at threonine 23. Mutation amino acid blocks These findings indicate part a signalling pathway inducing key immune responses.