Woronicz J D, Gao X, Cao Z, Rothe M, Goeddel D V
Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.
Science. 1997 Oct 31;278(5339):866-9. doi: 10.1126/science.278.5339.866.
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.
炎性细胞因子对转录因子核因子κB（NF-κB）的激活需要NF-κB诱导激酶（NIK）和IκB激酶α（IKK-α）的相继作用。一种广泛表达的蛋白激酶被鉴定出来，它与IKK-α有52%的同源性。IκB激酶β（IKK-β）在过表达时激活NF-κB，并使IκB-α的丝氨酸残基32和36以及IκB-β的丝氨酸19和23磷酸化。IKK-β的活性受到肿瘤坏死因子和白细胞介素-1处理的刺激。IKK-α和IKK-β形成与NIK相互作用的异二聚体。催化失活形式的IKK-β的过表达阻断了细胞因子诱导的NF-κB激活。因此，一个活性IκB激酶复合物可能需要三种不同的蛋白激酶。
