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

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

Related Species

Human immunodeficiency virus 1, Influenza A virus, Human SARS coronavirus, Severe acute respiratory syndrome coronavirus 2

Compartment

endosome membrane, cytosol

ReviewStatus

5/5

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

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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
12138165	Identification of threonine 66 as a functionally critical residue of the Dower, S, Volpe, F, Ross, K, Guesdon, F, Yang, L	J Biol Chem	2002
8837778	TRAF6 is a signal transducer for interleukin-1 Cao, Z, Kurama, T, Xiong, J, Takeuchi, M, Goeddel, DV	Nature	1996
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 Vologodskaia, M, Kobayashi, T, Wu, H, Cirilli, M, Lamothe, B, Arron, JR, Pike, JW, Ye, H, Shevde, NK, Choi, Y, Yim, M, Darnay, BG, Du, K, Dzivenu, OK, Segal, D, Singh, S	Nature	2002