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

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
Participants
Input
Output
Participates
as an event of
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 (Mus musculus)
K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Rattus norvegicus)
K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta (Sus scrofa)
Authored
Garapati, P V  (2014-07-14)
Reviewed
Geijtenbeek, TB  (2014-09-02)
Created
Garapati, P V  (2014-07-14)
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