◀ Back to TLR4
TLR4 — TRAF6
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
O/k complex ()
→
Complex of MYD88-TLR4-TRAF6
(increases, MYD88/TLR4/TRAF6 Activity)
Lee et al., J Biol Chem 2003*
Evidence: MyD88 is known as an immediate downstream adaptor molecules that interacts directly with TIR domain of TLRs. MyD88 recruits Il1 receptor-associated kinase (Irak) and Traf6 leading to activation of NFkB and MAPKs.
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BioCarta nf-kb signaling pathway:
LPS/TLR4/TLR4/MYD88/IRAK/TRAF6 complex (TLR4-MYD88-IRAK1-TRAF6)
→
IKK-alpha/MEKK1/NIK complex (CHUK-MAP3K1-MAP4K4)
(modification, activates)
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BioCarta toll-like receptor pathway:
LPS/TLR4/TLR4/TIRAP/TOLLIP/PKR/MYD88/IRAK/MD-2/CD14 complex (EIF2AK2-MYD88-CD14-TLR4-TOLLIP-TIRAP-IRAK1-LY96)
→
TRAF6
(modification, activates)
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BioCarta nf-kb signaling pathway:
TLR4/TLR4/MYD88/IRAK/TRAF6 complex (TLR4-MYD88-IRAK1-TRAF6)
(modification, collaborate)
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BioCarta nf-kb signaling pathway:
TLR4/TLR4/MYD88/IRAK/TRAF6 complex (TLR4-MYD88-IRAK1-TRAF6)
→
LPS/TLR4/TLR4/MYD88/IRAK/TRAF6 complex (TLR4-MYD88-IRAK1-TRAF6)
(modification, collaborate)
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BioCarta nf-kb signaling pathway:
None
→
LPS/TLR4/TLR4/MYD88/IRAK/TRAF6 complex (TLR4-MYD88-IRAK1-TRAF6)
(modification, collaborate)
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Reactome Reaction:
TLR4
→
TRAF6
(indirect_complex)
Deng et al., Cell 2000, Ross et al., J Biol Chem 2002, Ye et al., Nature 2002, Kaiser et al., J Immunol 2005, Häcker et al., Nature 2006, Lamothe et al., J Biol Chem 2007, Muroi et al., J Leukoc Biol 2008, Sasai et al., Mol Immunol 2010*, Cao et al., Nature 1996, Arch et al., Genes Dev 1998
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Reactome Reaction:
TLR4
→
TRAF6
(reaction)
Kishimoto et al., J Biol Chem 2000, Deng et al., Cell 2000, Ross et al., J Biol Chem 2002, Ye et al., Nature 2002, Jiang et al., Mol Cell Biol 2002, Jiang et al., J Biol Chem 2003, Kollewe et al., J Biol Chem 2004, Kaiser et al., J Immunol 2005, Sato et al., Nat Immunol 2005, Shim et al., Genes Dev 2005, Häcker et al., Nature 2006, Adhikari et al., Oncogene 2007, Gottipati et al., Cell Signal 2008, Muroi et al., J Leukoc Biol 2008, Sasai et al., Mol Immunol 2010*, Cao et al., Nature 1996, Arch et al., Genes Dev 1998
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WikiPathways Simplified Depiction of MYD88 Distinct Input-Output Pathway:
TLR1/TLR2/TLR4/TLR5/TLR6/TLR7/TLR8/TLR9/TLR10/IL1A
→
Complex of UBE2N-UBE2V1-TRAF6-TIFA-IRAK1
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Vivarelli et al., J Exp Med 2004
:
Since TRAF2 and
TRAF6 play important roles in CD40 signaling and TRAF6
plays an important role in
TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4
Zhang et al., Infect Immun 2005
(Pseudomonas Infections) :
We also determined that MyD88, IRAK,
TRAF6 , and Toll interacting protein (Tollip), but not TIRAP, were involved in the
TLR mediated response to P. aeruginosa in HAECs
Loniewski et al., Mol Immunol 2007
:
However, an essential
role of
TRAF6 in
TLR4 signaling and cytokine production is slightly controversial
Leppert et al., J Immunol 2007
:
The soluble variant surface glycoprotein of African trypanosomes is recognized by a macrophage scavenger receptor and induces I kappa B alpha degradation independently of
TRAF6 mediated
TLR signaling ... Activation of RAW 264.7 cells by sVSG following treatment of the cells with the TRAF6 inhibitory peptide DIVK resulted in enhanced NF-kappaB signaling, suggesting both that
TRAF6 dependent
TLR activation of the pathway alone is not required for signaling and that TLR pathway components may negatively regulate expression of sVSG induced signaling
Chen et al., Cell Signal 2008
:
Syntenin negatively regulates
TRAF6 mediated
IL-1R/TLR4 signaling
Verstak et al., J Biol Chem 2009
(Bacterial Infections...) :
We found that Mal and
TRAF6 directly interact in
response to TLR2 and
TLR4 stimulation, although membrane localization is not necessary to facilitate interaction
Kar et al., Eur J Immunol 2011
(Inflammation...) :
Analysis of upstream signaling events revealed that
TLR 2/4 mediated MyD88 dependent participation of IL-1R activated kinase (IRAK)1, TNF receptor associated factor
(TRAF)6 and TGFß activated kinase (TAK)1 is essential to induce cystatin mediated I?B kinase ( IKK ) /NF-?B activation in macrophages
Clark et al., Proc Natl Acad Sci U S A 2011
:
Toll-like receptor ( TLR ) ligands that signal via TIR-domain containing adapter inducing IFNß ( TRIF )
activate the I?B kinase ( IKK ) -related kinases,
TRAF associated NF?B activator ( TANK) binding kinase-1 (TBK1 ) and IKKe, which then phosphorylate IRF3 and induce the production of IFNß
Jono et al., PloS one 2012
(MAP Kinase Signaling System) :
PKC? synergizes with
TLR dependent
TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1
Inomata et al., Biochem Biophys Res Commun 2013
:
Furthermore, Atg5 deficiency increased formation of the
MyD88-TRAF6 signaling complex
induced by
TLR stimulation, and it enhanced activation of NF-?B signaling but not MAPKs and Akt