Activation of TAK1 complex bound to pUb-TRAF6

Stable Identifier
R-HSA-2730900
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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Binding of TAB2 and TAB3 to K63-linked polyubiquitin chains leads to the activation of TAK1 by an uncertain mechanism. Phosphorylation of TAK1 within the activation loop of the kinase is absolutely required for TAK1 activity. TAB1 is known to augment TAK1 catalytic activity by mediating spontaneous oligomerization and induces autophosphorylation of TAK1 (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 leads to the activation of TAK1. Some biochemical studies revealed that free K63 polyubiquitin chains, which are not conjugated to any cellular protein, can directly activate the TAK1 kinase complex (Xia 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
10838074 Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1

Sakurai, H, Miyoshi, H, Mizukami, J, Sugita, T

FEBS Lett. 2000
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
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
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Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:TAK1:TAB1:TAB2/3 [plasma membrane]
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Activity
Orthologous Events
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Created