Reactome | Activation of TAK1 complex bound to pUb-TRAF6

Activation of TAK1 complex bound to pUb-TRAF6

Stable Identifier

R-HSA-2730900

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Activation of TAK1 complex bound to pUb-TRAF6

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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
10838074	Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1 Sugita, T, Sakurai, H, Mizukami, J, Miyoshi, H	FEBS Lett.	2000
17496917	Ubiquitin-mediated activation of TAK1 and IKK Xu, M, Adhikari, A, Chen, ZJ	Oncogene	2007
16186825	Essential function for the kinase TAK1 in innate and adaptive immune responses Kawai, T, Takeuchi, O, Sanjo, H, Takeda, K, Ninomiya-Tsuji, J, Sato, S, Yamamoto, M, Akira, S, Matsumoto, K	Nat Immunol	2005
10702308	TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop Kishimoto, K, Ninomiya-Tsuji, J, Matsumoto, K	J Biol Chem	2000