Peters R T, Liao S M, Maniatis T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Mol Cell. 2000 Mar;5(3):513-22. doi: 10.1016/s1097-2765(00)80445-1.
Here we report the identification of a novel PMA-inducible IkappaB kinase complex, distinct from the well-characterized high-molecular weight IkappaB kinase complex containing IKKalpha, IKKbeta, and IKKgamma. We have characterized one kinase from this complex, which we designate IKKepsilon. Although recombinant IKKepsilon directly phosphorylates only serine 36 of IKBalpha, the PMA-activated endogenous IKKepsilon complex phosphorylates both critical serine residues. Remarkably, this activity is due to the presence of a distinct kinase in this complex. A dominant-negative mutant of IKKepsilon blocks induction of NF-kappaB by both PMA and activation of the T cell receptor but has no effect on the activation of NF-KB by TNFalpha or IL-1. These observations indicate that the activation of NF-kappaB requires multiple distinct IkappaB kinase complexes, which respond to both overlapping and discrete signaling pathways.
我们在此报告鉴定出一种新型的佛波酯（PMA）诱导型IκB激酶复合物，它不同于已被充分表征的包含IKKα、IKKβ和IKKγ的高分子量IκB激酶复合物。我们已对该复合物中的一种激酶进行了表征，将其命名为IKKε。尽管重组IKKε仅直接磷酸化IκBα的丝氨酸36，但PMA激活的内源性IKKε复合物可磷酸化两个关键的丝氨酸残基。值得注意的是，这种活性归因于该复合物中存在一种独特的激酶。IKKε的显性负性突变体可阻断PMA和T细胞受体激活对NF-κB的诱导，但对TNFα或IL-1激活NF-κB没有影响。这些观察结果表明，NF-κB的激活需要多种不同的IκB激酶复合物，它们对重叠和离散的信号通路均有反应。
