IKK epsilon is recruited to the Viral dsRNA:TLR3:TICAM1 complex

Stable Identifier
R-GGA-433804
Type
Reaction [binding]
Species
Gallus gallus
Related Species
Infectious bronchitis virus
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Chicken IKK epsilon protein, confirmed by transcript evidedence, shows 68% amino acid sequence identity to its human ortholog. Upon stimulation by pathogen-associated inflammatory signals, TANK-binding kinase 1 (TBK1) and inhibitor of kappaB kinase epsilon (IKKi, IKBKE) induce type I interferon expression and modulate nuclear factor kappa-B (NF-kappa-B) signaling (Fitzgerald KA et al. 2003; Hemmi H et al. 2004). The structural studies of TBK1 revealed a dimeric assembly which is mediated by several interfaces involving kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD) of TBK1 (Larabi A et al. 2013; Tu D et al. 2013). ULD of TBK1 (and IKBKE) was involved in the control of kinase activation, substrate presentation and downstream signaling (Ikeda F et al 2007; Tu D et al. 2013). An intact TBK1 dimer was a subject to K63-linked polyubiquitination on lysines 30 and 401 (Tu D et al. 2013). Activation of TBK1 rearranged the KD into an active conformation while maintaining the overall dimer conformation (Larabi A et al. 2013). The ubiquitination sites and dimer contacts are conserved in the close homolog IKBKE (Tu D et al. 2013). The activation of TBK1 and IKKi may occur through autophosphorylation or via activity of a distinct protein kinase (Clark et al. 2009). Other studies demonstrated an essential role of TRAF3 in the activation of TBK1 (Hacker et al 2006). TBK1 and IKBKE were found to interact with scaffold proteins TANK (TRAF family member associated NFkB activator), NAP1 (NAK-associated protein 1), SINTBAD (similar to NAP1 TBK1 adaptor) which connect TBK1/IKBKE to pathogen-activated signaling cascades (Pomerantz JL and Baltimore D 1999; Guo B and Cheng G 2007; Gatot JC et al. 2007; Ryzhakov G and Randow F 2007; Goncalves A et al. 2011).
Literature References
PubMed ID Title Journal Year
17599067 Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes

Dötsch, V, Rozenknop, A, Rogov, V, Nordmeier, RD, Ikeda, F, Akira, S, Dikic, I, Hecker, CM, Hofmann, K

EMBO J 2007
19307177 Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation

Plater, L, Peggie, M, Clark, K, Cohen, P

J Biol Chem 2009
Participants
Participates
Inferred From
Authored
Reviewed
Created
Cite Us!