Activated TAK1 mediates phosphorylation of the IKK Complex

Stable Identifier
R-HSA-168184
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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In humans, the IKKs - IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. The IKK complex contains two catalytic subunits, IKK alpha and IKK beta associated with a regulatory subunit, NEMO (IKKgamma). The activation of the IKK complex and the NFkB mediated antiviral response are dependent on the phosphorylation of IKK alpha/beta at its activation loop and the ubiquitination of NEMO [Solt et al 2009; Li et al 2002]. NEMO ubiquitination by TRAF6 is required for optimal activation of IKKalpha/beta; it is unclear if NEMO subunit undergoes K63-linked or linear ubiquitination.

This basic trimolecular complex is referred to as the IKK complex. Each catalytic IKK subunit has an N-terminal kinase domain and leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-terminal 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 and thus activates the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.

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

Adhikari, A, Xu, M, Chen, ZJ

Oncogene 2007
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK

Wang, C, Deng, L, Hong, M, Akkaraju, GR, Inoue, J, Chen, ZJ

Nature 2001
9744859 Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death

Arch, RH, Gedrich, RW, Thompson, CB

Genes Dev 1998
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
MAP kinase kinase kinase activity of Activated TAK complexes [cytosol]
Physical Entity
Activity
Orthologous Events
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Created