Activation of recruited TAK1 within the activated TLR3 complex

Stable Identifier
R-HSA-177692
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Compartment
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TAK1 complex consists of transforming growth factor-beta (TGFB)-activated kinase (TAK1) and TAK1-binding protein 1 (TAB1), TAB2 and TAB3. TAK1 requires TAB1 for its kinase activity (Shibuya et al. 1996, Sakurai et al. 2000). TAB1 promotes TAK1 autophosphorylation at the kinase activation lobe, probably through an allosteric mechanism (Brown et al. 2005, Ono et al. 2001). The TAK1 complex is regulated by polyubiquitination. Binding of TAB2 and TAB3 to Lys63-linked polyubiquitin chains leads to the activation of TAK1 by an uncertain mechanism. Binding of multiple TAK1 complexes to the same polyubiquitin chain may promote oligomerization of TAK1, facilitating TAK1 autophosphorylation and subsequent activation of its kinase activity (Kishimoto et al. 2000). The binding of TAB2/3 to polyubiquitinated TRAF6 may facilitate polyubiquitination of TAB2/3 by TRAF6 (Ishitani et al. 2003), which might result in conformational changes within the TAK1 complex that lead to TAK1 activation. Another possibility is that TAB2/3 may recruit the IKK complex by binding to ubiquitinated NEMO; polyubiquitin chains may function as a scaffold for higher order signaling complexes that allow interaction between TAK1 and IKK (Kanayama et al. 2004).

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

Adhikari, A, Xu, M, Chen, ZJ

Oncogene 2007
12609980 Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR

Jiang, Z, Zamanian-Daryoush, M, Nie, H, Silva, AM, Williams, BR, Li, X

J Biol Chem 2003
16186825 Essential function for the kinase TAK1 in innate and adaptive immune responses

Sato, S, Sanjo, H, Takeda, K, Ninomiya-Tsuji, J, Yamamoto, M, Kawai, T, Matsumoto, K, Takeuchi, O, Akira, S

Nat Immunol 2005
16260493 TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Shim, JH, Xiao, C, Paschal, AE, Bailey, ST, Rao, P, Hayden, MS, Lee, KY, Bussey, C, Steckel, M, Tanaka, N, Yamada, G, Akira, S, Matsumoto, K, Ghosh, S

Genes Dev 2005
10702308 TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop

Kishimoto, K, Matsumoto, K, Ninomiya-Tsuji, J

J Biol Chem 2000
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
MAP kinase kinase kinase kinase activity of viral dsRNA:TLR3:TRIF:polyUb-TRAF6:TAK1:TAB1:TAB2/TAB3: free polyUb chain [endosome membrane]
Physical Entity
Activity
Orthologous Events
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Created