Reactome | K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta

Stable Identifier

R-HSA-5607742

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta

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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 Wang, C, Deng, L, Hong, M, Akkaraju, GR, Inoue, J, Chen, ZJ	Nature	2001
14514672	Signal-induced ubiquitination of I kappaB Kinase-beta Carter, RS, Pennington, KN, Ungurait, BJ, Arrate, P, Ballard, DW	J. Biol. Chem.	2003
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

Input

Output

Participates

as an event of

CLEC7A (Dectin-1) signaling (Homo sapiens)

Catalyst Activity

protein serine/threonine kinase activity of p-T231-CARD9:BCL10:MALT1:K63polyUb-TRAF6 oligomers:TAB1:TAB2/TAB3:K63polyUb-34,158-p3Y,1S-TAK1 [plasma membrane]

Physical Entity

p-T231-CARD9:BCL10:MALT1:K63polyUb-TRAF6 oligomers:TAB1:TAB2/TAB3:K63polyUb-34,158-p3Y,1S-TAK1 [plasma membrane] (Homo sapiens)

Activity

protein serine/threonine kinase activity (GO:0004674)

Orthologous Events

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Bos taurus)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Canis familiaris)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Gallus gallus)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Mus musculus)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Rattus norvegicus)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Sus scrofa)

K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Xenopus tropicalis)