NFKB p105, TPL2 (COT) and ABIN2 form a stable complex

Stable Identifier
R-HSA-451634
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Degradation of NFKB p105 frees Tpl2 from p105 allowing it to activate MEK1. The C-terminal half of NFKB1 p105 forms a high-affinity stoichiometric association with MAP3K8 (TPL2) via two distinct interactions (Belich et al. 1999; Beinke et al. 2003). The Tpl2 C-terminus (residues 398-467) binds to a region N-terminal to the p105 ankyrin repeat region (human p105 residues 497-534), whereas the Tpl2 kinase domain interacts with the p105 death domain (Beinke et al. 2003). In unstimulated macrophages, all detectable Tpl2 is associated with p105 (Belich et al. 1999; Lang et al. 2004). Binding to p105 maintains the stability of Tpl2 but inhibits Tpl2 MEK kinase activity by preventing access to MEK (Beinke et al. 2003; Waterfield et al. 2003). Tpl2 phosphorylation at Thr-290 may also play a role in the activation of Tpl2 (Cho & Tsichlis 2005).

A20-binding inhibitor of NFkappaB2 (ABIN-2 ot TNIP2) interacts with Tpl2 and p105 but preferentially forms a ternary complex with both proteins. As ABIN2 is a polyubiquitin binding protein, it has been suggested that it may facilitate recruitment of the p105/Tpl2 complex to the activated IKK complex, allowing IKK2 induced p105 phosphorylation and consequent Tpl2 activation.
Literature References
PubMed ID Title Journal Year
12832462 NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity

Belich, MP, Ley, SC, Gamblin, SJ, Beinke, S, Smerdon, SJ, Walker, PA, Lang, V, Deka, J, Howell, S

Mol Cell Biol 2003
9950430 TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105

Belich, MP, Ley, SC, Salmeron, A, Johnston, LH

Nature 1999
15169888 ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability

Ley, SC, Symons, A, Janzen, J, Beinke, S, Watton, SJ, Lang, V, Soneji, Y, Howell, S

Mol Cell Biol 2004
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
3xUb-p-S927,S932-NFKB1(1-968) [cytosol] (Homo sapiens)
Regulator
3xUb, 2xp-S-NFKB1(1-968):p-S,T-MAP3K8:TNIP2 [cytosol] (Homo sapiens)
Orthologous Events
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Bos taurus)
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Canis familiaris)
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Gallus gallus)
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Mus musculus)
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Sus scrofa)
NFKB p105, TPL2 (COT) and ABIN2 form a stable complex (Xenopus tropicalis)
Authored
Ray, KP  (2010-05-17)
Reviewed
Pinteaux, E  (2010-05-17)
DeCicco-Skinner, KL  (2015-08-21)
Created
Jupe, S  (2010-01-07)
Cite Us!