Science · 1997 · 1.2K citations · 14 references
Life SciencesCell BiologyMolecular BiologyCell SignalingMolecular Cell BiologySignal TransductionCytokine BiologyCytokine SignalingInflammatory Cell ResponsesInflammatory Cell SignalingInflammatory SignalingProtein Kinase CascadesMacromolecular Complex FormationNf-κb SignalingNuclear Factor Kappa B ActivationNuclear Factor Kappa B ModulationNuclear Factor Kappa B SignalingNuclear Factor Kappa B Signaling ComplexesProtein Kinase B Signaling
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.
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.
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Patrick A. Baeuerle, David Baltimore · Cell · 1996 · 3K citations · Full text
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
Joseph A. DiDonato, Makio Hayakawa, David M. Rothwarf et al. · Nature · 1997 · 2.1K citations
TRAF6 is a signal transducer for interleukin-1
Zhaodan Cao, Jessie Xiong, Masahiro Takeuchi et al. · Nature · 1996 · 1.3K citations
Identification and Characterization of an IκB Kinase
Catherine H. Régnier, Ho Yeong Song, Xiong Gao et al. · Cell · 1997 · 1.2K citations · Full text