chicken RIP1 facilitates IKKs complex activation

Stable Identifier
Reaction [transition]
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
12221085 IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program

Li, X, Massa, PE, Hanidu, A, Peet, GW, Aro, P, Savitt, A, Mische, S, Li, J, Marcu, KB

J Biol Chem 2002
16115877 Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation

Cusson-Hermance, N, Khurana, S, Lee, TH, Fitzgerald, KA, Kelliher, MA

J Biol Chem 2005
15145317 The two NF-kappaB activation pathways and their role in innate and adaptive immunity

Bonizzi, G, Karin, M

Trends Immunol 2004
19666475 The nemo binding domains of both IKKalpha and IKKbeta regulate IKK complex assembly and classical NFkappaB activation

Solt, LA, Madge, LA, May, MJ

J Biol Chem 2009
Catalyst Activity

protein serine/threonine kinase activity of Activated chicken TAK1 complexes [cytosol]

This event is regulated
Inferred From
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