chicken RIP1 facilitates IKKs complex activation

The 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 the NFkB mediated antiviral response are dependent on the phosphorylation of IKK alpha/beta at its activation loop and the K63-linked ubiquitination of NEMO[Solt et al 2009; Li et al 2002]. NEMO ubiquitination by TRAF6 is required for optimal activation of IKKalpha/beta. This basic trimolecular complex is referred to as the IKK complex. <p>Each catalytic IKK subunit has an N-terminus kinase domain, a leucine zipper (LZ) motif, a helix-loop-helix (HLH) and a C-terminus NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs.<p>IKK beta is the major IKK catalytic subunit for NF-kB activation. Phosphorylation in the activation loop of IKK beta requires Ser177 and Ser181 (data for human proteins) and thus activates the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.<p>Chicken IKK alpha and IKK beta showed 81% and 68% identity to the corresponding human IKK kinases (UniProtKB sequence data using NCBI BLASTP 2.2.20). Multiple sequence alignment of the proteins by ClustalW demonstrated that chicken IKK alpha serine residues 190 and 194 correspond to human Ser176 and Ser180, that are required for the activation. It is unclear what serine residues of chicken IKK beta are involved into the phosphorylation.<p>Chicken IKK gamma or NEMO is considered as avian lost.[Cormican et al 2009].

IKKs（IkB激酶复合物）充当了多种刺激激活NF-kB的 master regulator。该复合物包含两个催化亚基，即IKK alpha和IKK beta，以及一个调节亚基，即IKKgamma/NEMO。IKK复合物的激活以及由NFkB介导的抗病毒反应依赖于IKK alpha/beta在其激活环上的磷酸化以及NEMO的K63连接泛素化[Solt等人，2009；Li等人，2002]。TRAF6介导的NEMO泛素化对于IKKalpha/beta的最佳激活是必需的。这个基本的三分子复合物被称为IKK复合物。<p>每个催化IKK亚基均具有一个N端激酶结构域、一个亮氨酸拉链（LZ）基序、一个螺旋-环-螺旋（HLH）和一个C端NEMO结合结构域（NBD）。IKK催化亚基通过其LZ基序进行二聚化。<p>IKK beta是NF-kB激活的主要IKK催化亚基。IKK beta的激活环上的磷酸化需要Ser177和Ser181（人类蛋白的数据）从而激活IKK激酶活性，导致IkB alpha磷酸化和NF-kB激活。<p>鸡IKK alpha和IKK beta与相应的人类IKK激酶（使用NCBI BLASTP 2.2.20的UniProtKB序列数据）的序列具有81%和68%的同源性。通过ClustalW对蛋白质进行多序列比对显示，鸡IKK alpha的Ser190和Ser194残基对应于人类所需的Ser176和Ser180残基，这些残基对于激活是必需的。至于鸡IKK beta中参与磷酸化的丝氨酸残基尚不明确。<p>鸡IKK gamma或NEMO被认为是禽类丢失的。[Cormican等人，2009]。