IκB Kinase-β: NF-κB Activation and Complex Formation with IκB Kinase-α and NIK

TLDR

Activation of the transcription factor nuclear factor kappa B (NF‑κB) by inflammatory cytokines requires the successive action of NF‑κB‑inducing kinase (NIK) and IkappaB kinase‑alpha (IKK‑α). IkappaB kinase‑beta (IKK‑β) activated NF‑κB when overexpressed and phosphorylated serine residues 32 and 36 of IkappaB‑α and serines 19 and 23 of IkappaB‑β. Findings revealed a ubiquitously expressed kinase 52 % identical to IKK‑α, that IKK‑β activity is up‑regulated by TNF and IL‑1, that IKK‑α and IKK‑β heterodimerize with NIK, and that a catalytically inactive IKK‑β blocks cytokine‑induced NF‑κB activation, suggesting an active IKK complex requires three distinct kinases.

Abstract

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) by inflammatory cytokines requires the successive action of NF-kappaB-inducing kinase (NIK) and IkappaB kinase-alpha (IKK-alpha). A widely expressed protein kinase was identified that is 52 percent identical to IKK-alpha. IkappaB kinase-beta (IKK-beta) activated NF-kappaB when overexpressed and phosphorylated serine residues 32 and 36 of IkappaB-alpha and serines 19 and 23 of IkappaB-beta. The activity of IKK-beta was stimulated by tumor necrosis factor and interleukin-1 treatment. IKK-alpha and IKK-beta formed heterodimers that interacted with NIK. Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappaB activation. Thus, an active IkappaB kinase complex may require three distinct protein kinases.