TRAF6 binds to hp- IRAK1/or p-IRAK2:p-IRAK4:MyD88:activated TLR7/8 or 9

Stable Identifier
R-HSA-975111
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Hyperphosphorylated IRAK1, still within the receptor complex, binds TRAF6 through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain (Li et al. 2001). The C-terminal region of IRAK-1 contains three potential TRAF6-binding sites; mutation of the amino acids (Glu544, Glu587, Glu706) in these sites to alanine greatly reduces activation of NFkappaB (Ye et al. 2002).

IRAK-2 has two TRAF6 binding motifs that are responsible for initiating TRAF6 signaling transduction (Ye H et al 2002). IRAK2 point mutants with mutated TRAF6-binding motifs abrogate NFkB activation and are incapable to stimulate TRAF6 ubiquitination (Keating SE et al 2007).

Literature References
PubMed ID Title Journal Year
8837778 TRAF6 is a signal transducer for interleukin-1

Cao, Z, Xiong, J, Takeuchi, M, Kurama, T, Goeddel, DV

Nature 1996
12138165 Identification of threonine 66 as a functionally critical residue of the

Ross, K, Yang, L, Dower, S, Volpe, F, Guesdon, F

J Biol Chem 2002
18070982 TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB

Muroi, M, Tanamoto, K

J Leukoc Biol 2008
12140561 Distinct molecular mechanism for initiating TRAF6 signalling

Ye, H, Arron, JR, Lamothe, B, Cirilli, M, Kobayashi, T, Shevde, NK, Segal, D, Dzivenu, OK, Vologodskaia, M, Yim, M, Du, K, Singh, S, Pike, JW, Darnay, BG, Choi, Y, Wu, H

Nature 2002
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