K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta

In humans, the 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 is dependent on the phosphorylation of IKK alpha/beta at its activation loop and the K63-linked ubiquitination of NEMO. This basic trimolecular complex is referred to as the IKK complex. <br>IKK subunits have 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. IKK beta is the major IKK catalytic subunit for NF-kB activation. Activated TAK1 phosphorylate IKK beta on S177 and S181 (S176 and S180 in IKK alpha) in the activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.

在人类中，IkB激酶（IKK）复合体充当了由多种刺激激活NF-kB的主导调节因子。该复合体包含两个催化亚基，即IKKα和IKKβ，以及一个调节亚基，即IKKgamma/NEMO。IKK复合体的激活依赖于IKKα/β在其激活环上的磷酸化以及NEMO的K63连接泛素化。这一基本的三角形三分子复合体被称为IKK复合体。IKK亚基具有N端激酶结构域、亮氨酸拉链（LZ）基序、螺旋-环-螺旋（HLH）和C端NEMO结合域（NBD）。IKK催化亚基通过其LZ基序形成二聚体。IKKβ是NF-kB激活的主要IKK催化亚基。激活的TAK1在S177和S181（IKKα中的S176和S180）位点对IKKβ进行磷酸化，从而激活IKK激酶活性，导致IkBα磷酸化和NF-kB激活。