Activation of IKK by MEKK1

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.

在人类中，IkB激酶（IKK）复合体充当多种刺激激活NF-kB的 master regulator。该复合体包含两个催化亚基，即IKK α和IKK β，以及一个调节亚基，即IKKgamma/NEMO。IKK复合体的激活以及由NFkB介导的抗病毒反应依赖于IKK α/β在其激活环上的磷酸化和NEMO的泛素化。[Solt等，2009年；Li等，2002年]。由TRAF6介导的NEMO泛素化对于IKKα/β的最佳激活是必需的；然而，NEMO亚基是否经历K63链接或线性泛素化仍不清楚。<br><br>这一基本的三分子复合体被称为IKK复合体。每个催化IKK亚基都具有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基序二聚化。<br><br>IKK β是NF-kB激活的主要IKK催化亚基。MEKK1可以在体内激活IKK-α（IKKA）和IKK-β（IKKB）。MEKK1在IKKA的激活环中磷酸化Ser-176和Ser-180，在IKKB中磷酸化Ser-177和Ser-181，从而激活IKK激酶活性，导致IkB α磷酸化和NF-kB激活。