Phosphorylation of IKKs complex by activated TAK1

Stable Identifier
R-GGA-433955
Type
Reaction [transition]
Species
Gallus gallus
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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.

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.

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.

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.

Chicken IKK gamma or NEMO is considered as avian lost.[Cormican et al 2009].

Literature References
PubMed ID Title Journal Year
17496917 Ubiquitin-mediated activation of TAK1 and IKK

Adhikari, A, Xu, M, Chen, ZJ

Oncogene 2007
17047224 Regulation and function of IKK and IKK-related kinases

Hacker, H, Karin, M

Sci STKE 2006
17332413 Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity

Tenoever, BR, Ng, SL, Chua, MA, McWhirter, SM, Garcia-Sastre, A, Maniatis, T

Science 2007
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Catalyst Activity
Title
protein serine/threonine kinase activity of Activated chicken TAK1 complexes [cytosol]
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