Active IKK Complex phosphorylates NF-kappa-B inhibitor

In human, IkBs (NFKBIA, NFKBIB or NFKBIE) are inhibitory proteins that sequesters NF-kappa-B in the cytoplasm, by masking a nuclear localization signal, located just at the C-terminal end of the RelA (p65) subunit of the RelA:NFKB1 heterodimer. <p>A key event in NF-kappa-B activation involves phosphorylation of IkB by an IkB kinase (IKK). The phosphorylation and ubiquitination of IkB kinase complex is mediated by two distinct pathways, either the classical or alternative pathway. In the classical NF-kappa-B signaling pathway, the activated IKK (IkB kinase) complex, predominantly acting through IKK beta (IKKb, IKBKB) in an IKK gamma (IKBKG, NEMO)-dependent manner, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of human NFKBIA (IkB-alpha) or Ser19 and Ser22 of NFKBIB (IkB-beta)). Once phosphorylated, IkB undergoes ubiquitin-mediated degradation, releasing NF-kappa-B.<br>

在人类中，IkBs（NFKBIA、NFKBIB或NFKBIE）是一类抑制蛋白，它们通过掩盖位于RelA（p65）亚基C端末端的核定位信号，将NF-κB隔离在细胞质中。NF-κB激活的关键事件之一涉及IkB（IκB）由IκB激酶（IKK）磷酸化。IkB激酶复合物的磷酸化和泛素化由两条不同的途径介导，即经典途径或替代途径。在经典NF-κB信号通路中，激活的IKK（IκB激酶）复合物，主要通过IKK β（IKKb、IKBKB）在IKK γ（IKBKG、NEMO）依赖性方式下发挥作用，催化IkBs（相当于人类NFKBIA（IkB-α）的Ser32和Ser36或NFKBIB（IkB-β）的Ser19和Ser22）的磷酸化。一旦磷酸化，IkB将经历泛素介导的降解，从而释放NF-κB。