Phosphorylation of IKK-beta by TAK1

Stable Identifier
R-HSA-2730876
Type
Reaction [transition]
Species
Homo sapiens
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In humans, the IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. It contains two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex is dependent on the phosphorylation of IKK alpha/beta at its activation loop and the K63-linked ubiquitination of NEMO. This basic trimolecular complex is referred to as the IKK complex.
IKK subunits have a N-term kinase domain a leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-ter 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. Activated TAK1 phosphorylate IKK beta on S177 and S181 (S176 and S180 in IKK alpha) in the activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.

Literature References
PubMed ID Title Journal Year
14514672 Signal-induced ubiquitination of I kappaB Kinase-beta

Carter, RS, Pennington, KN, Ungurait, BJ, Arrate, P, Ballard, DW

J. Biol. Chem. 2003
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
17047224 Regulation and function of IKK and IKK-related kinases

Hacker, H, Karin, M

Sci STKE 2006
20300203 The IKK complex, a central regulator of NF-kappaB activation

Israel, A

Cold Spring Harb Perspect Biol 2010
11325957 Persistent activation of NF-kappa B by the tax transforming protein involves chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma

Carter, RS, Geyer, BC, Xie, M, Acevedo-Suárez, CA, Ballard, DW

J. Biol. Chem. 2001
Participants
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Catalyst Activity
Title
protein serine/threonine kinase activity of DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:activated TAK1 complex [plasma membrane]
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Orthologous Events
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