Activated IKK Complex IKK complex Activation of IKK by MEKK1 Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 In Human, IKKs - IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. It contains two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex and NFkB mediated antiviral responce are dependent on the phosphorylation of IKK alpha/beta at its activation loop and the ubiquitination of NEMO.[Solt et al 2009]; [Li et al 2002]. NEMO ubiquitination by TRAF6 is required for optimal activation of IKKalpha/beta; it's remained unclear if NEMO subunit undergoes K63-linked or linear ubiquitination.<br><br>This basic trimolecular complex is referred to as the IKK complex. Each catalytic IKK subunit has a N-term kinase domain a leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-ter NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs.<br><br>IKK beta is the major IKK catalytic subunit for NF-kB activation. MEKK1 can activate both IKK-alpha (IKKA) and IKK-beta (IKKB) in vivo. MEKK1 phosphorylates Ser-176 and Ser-180 in IKKA and Ser-177 and Ser-181 in IKKB activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation. Pubmed12221085 Pubmed19666475 Pubmed9008162 Pubmed9689078 Reactome Database ID Release 43933530 Reactome, http://www.reactome.org ReactomeREACT_24935 Reviewed: Kawai, T, Akira, S, 2010-10-30 has a Stoichiometric coefficient of 4