Reactome | Phosphorylation of IKK-beta by TAK1

Phosphorylation of IKK-beta by TAK1

Stable Identifier

R-HSA-2730876

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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
11460167	TAK1 is a ubiquitin-dependent kinase of MKK and IKK Deng, L, Inoue, J, Akkaraju, GR, Hong, M, Wang, C, Chen, ZJ	Nature	2001
14514672	Signal-induced ubiquitination of I kappaB Kinase-beta Pennington, KN, Carter, RS, Ballard, DW, Arrate, P, Ungurait, BJ	J. Biol. Chem.	2003
17047224	Regulation and function of IKK and IKK-related kinases Karin, M, Hacker, H	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 Ballard, DW, Acevedo-Suárez, CA, Geyer, BC, Carter, RS, Xie, M	J. Biol. Chem.	2001