Senftleben U, Cao Y, Xiao G, Greten F R, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun S C, Karin M
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Science. 2001 Aug 24;293(5534):1495-9. doi: 10.1126/science.1062677.
In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.
在哺乳动物中，响应感染而激活的经典核因子κB（NF-κB）信号通路基于IκB抑制剂的降解。该通路依赖于IκB激酶（IKK），它包含两个催化亚基，即IKKα和IKKβ。IKKβ对于诱导性IκB磷酸化和降解至关重要，而IKKα并非如此。在此我们表明，IKKα对于B细胞成熟、次级淋巴器官的形成、某些NF-κB靶基因表达的增加以及NF-κB2（p100）前体的加工是必需的。IKKα优先磷酸化NF-κB2，并且这种活性需要其被上游激酶磷酸化，其中之一可能是NF-κB诱导激酶（NIK）。因此，IKKα是基于受调控的NF-κB2加工而非IκB降解的第二条NF-κB激活通路的关键组成部分。
