activated IKKs phosphorylates IkB alpha causing the NFkB complex to dissociate from the phospho-IkB

The phosphorylation and ubiquitination of IkB kinase complex is mediated by two distinct pathways, either the classical or alternative pathway. In the classical NF-kB signaling pathway, the activated IKK complex, predominantly acting through IKK beta in an IKK gamma-dependent manner, catalyzes the phosphorylation of IkBs (at sites corresponding to Ser32 and Ser36 of human IkB-alpha or Ser19 and Ser22 of human IkB-beta), polyubiquitination (at sites corresponding to Lys21 and Lys22 of human IkB-alpha) and subsequent degradation by the 26S proteasome. The K-48 ubiquitination is mediated by the E2 ubiquitin ligases (or SCFs) formed by three subunits: Skp1, Cul A (Cdc53), and one of many F-box proteins.<p>Chicken IkB-alpha shows 71% identity to the human IkB alpha kinase. Multiple sequence alignment of the human and chicken IKB-alpha showed that chicken Ser36 and Ser40 correspond to human Ser32 and Ser 36 mentioned above.<p>There is insufficient data for chicken IkB beta to make a comparison with other species.

IkB激酶复合物的磷酸化和泛素化过程由两条不同的途径介导，即经典途径或替代途径。在经典的NF-kB信号通路中，被激活的IKK复合物，主要通过IKK beta在IKK gamma依赖的方式下发挥作用，催化IkB（对应于人类IkB-α的Ser32和Ser36或人类IkB-β的Ser19和Ser22位点）的磷酸化、多泛素化（对应于人类IkB-α的Lys21和Lys22位点）以及随后的由26S蛋白酶体介导的降解。K-48泛素化由由三个亚基——Skp1、Cul A（Cdc53）以及众多F-box蛋白之一形成的E2泛素连接酶（或SCFs）介导。鸡IkB-α与人类IkB-α激酶具有71%的同源性。人类与鸡IKB-α的多序列比对显示，鸡Ser36和Ser40对应于上述提及的人类Ser32和Ser36。关于鸡IkB-β，由于缺乏足够的数据，无法与其他物种进行比较。