NFkB Complex IkBs:NFkB Phospho-NF-kappaB Inhibitor Phospho-IKK Complex phosphorylates IkB within the IkB:NFkB Complex EC Number: 2.7.11 Edited: Shamovsky, V, 2009-12-16 In human, IkB is an inhibitory protein that sequesters NF-kB in the cytoplasm, by masking a nuclear localization signal, located just at the C-terminal end in each of the NF-kB subunits. <p>A key event in NF-kB 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-kB signaling pathway, the activated IKK (IkB kinase) complex, predominantly acting through IKK beta in an IKK gamma-dependent manner, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of human IkB-alpha or Ser19 and Ser22 of human IkB-beta); Once phosphorylated, IkB undergoes ubiquitin-mediated degradation, releasing NF-kB. Pubmed10723127 Pubmed12221085 Pubmed17047224 Pubmed19666475 Reactome Database ID Release 43168140 Reactome, http://www.reactome.org ReactomeREACT_6848 Reviewed: D'Eustachio, P, 2011-12-07 Reviewed: Fitzgerald, Katherine A, 2012-11-13 Reviewed: Napetschnig, Johanna, 2012-11-16 Reviewed: Upton, JW, Mocarski, ES, 2012--0-2- has a Stoichiometric coefficient of 4