◀ Back to TLR4
IRAK1 — TLR4
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
IRAK1
→
TLR4
(increases, TLR4 Activity, IRAK1 Activity)
Evidence: CSM-induced activation of TLR-4 has been shown to induce IRAK1 phosphorylation and TRAF6 degradation. An increase in IkB phosphorylation and degradation is also observed which ultimately leads to the translocation of NF-kB (p65) into the nucleus. The ability of cigarette smoke condensate (CSC) to activate NF-kB has also been demonstrated in another study using U937 cells. CSC has been shown to induce the activation of IKK (-a and -b) at 15 minutes post treatment, which resulted in increased phos...
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OpenBEL Selventa BEL large corpus:
O/k complex ()
→
Complex of IRAK1-MYD88-TLR4
(increases, IRAK1/MYD88/TLR4 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:
CD14
→
LPS/TLR4/TLR4/TIRAP/TOLLIP/PKR/MYD88/IRAK/MD-2/CD14 complex (EIF2AK2-MYD88-CD14-TLR4-TOLLIP-TIRAP-IRAK1-LY96)
(modification, collaborate)
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BioCarta toll-like receptor pathway:
CD14
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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BioCarta toll-like receptor pathway:
None
→
LPS/TLR4/TLR4/TIRAP/TOLLIP/PKR/MYD88/IRAK/MD-2/CD14 complex (EIF2AK2-MYD88-CD14-TLR4-TOLLIP-TIRAP-IRAK1-LY96)
(modification, collaborate)
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BioCarta toll-like receptor pathway:
None
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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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)
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
LPS/TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2/CD14/LBP complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2-EHHADH-CD14)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
LPS/TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2/CD14/LBP complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2-EHHADH-CD14)
→
CD14/LBP complex (CD14-EHHADH)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
LPS/TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2/CD14/LBP complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2-EHHADH-CD14)
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
None
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
CD14/LBP complex (CD14-EHHADH)
→
TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2 complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2)
(modification, collaborate)
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BioCarta inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages:
LPS/TLR4/TLR4/TIRAP/TOLLIP/MYD88/IRAK/PKR/MD-2/CD14/LBP complex (IRAK1-LY96-TIRAP-TLR4-TOLLIP-MYD88-EIF2AK2-EHHADH-CD14)
(ceramide biosynthetic process, 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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NCI Pathway Database Endogenous TLR signaling:
IRAK2 (IRAK2)
→
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP/IRAK/IRAK2/IRAK4 complex (TLR4-LY96-HMGB1-IRAK1-IRAK2-IRAK4-MYD88-TIRAP)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
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NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
→
IRAK (IRAK1)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
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NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
→
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP/IRAK/IRAK2/IRAK4 complex (TLR4-LY96-HMGB1-IRAK1-IRAK2-IRAK4-MYD88-TIRAP)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
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NCI Pathway Database Endogenous TLR signaling:
IRAK4 (IRAK4)
→
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP/IRAK/IRAK2/IRAK4 complex (TLR4-LY96-HMGB1-IRAK1-IRAK2-IRAK4-MYD88-TIRAP)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
-
NCI Pathway Database Endogenous TLR signaling:
IRAK (IRAK1)
→
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP/IRAK/IRAK2/IRAK4 complex (TLR4-LY96-HMGB1-IRAK1-IRAK2-IRAK4-MYD88-TIRAP)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
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NCI Pathway Database Endogenous TLR signaling:
MRP8/MRP14/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-MYD88-TIRAP-S100A8-S100A9)
→
IRAK (IRAK1)
(modification, activates)
Vogl et al., Nat Med 2007
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Reactome Reaction:
TLR4
→
IRAK1
(reaction)
Li et al., Proc Natl Acad Sci U S A 2002, Kollewe et al., J Biol Chem 2004, Rao et al., Mol Cell Biol 2005, Keating et al., J Biol Chem 2007, Gottipati et al., Cell Signal 2008, Wan et al., J Biol Chem 2009, Lin et al., Nature 2010, Flannery et al., J Biol Chem 2011
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Reactome Reaction:
TLR4
→
IRAK1
(indirect_complex)
Li et al., Proc Natl Acad Sci U S A 2002, Kollewe et al., J Biol Chem 2004, Rao et al., Mol Cell Biol 2005, Keating et al., J Biol Chem 2007, Gottipati et al., Cell Signal 2008, Wan et al., J Biol Chem 2009, Lin et al., Nature 2010, Flannery et al., J Biol Chem 2011
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WikiPathways ApoE and miR-146 in inflammation and atherosclerosis:
TLR4
→
IRAK1/TRAF4
(mim-binding)
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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)
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WikiPathways TLR4 Signaling and Tolerance:
Complex of TIRAP-MAL-TRAM1-TLR4
→
Complex of IRAK1-MYD88-IRAK4
(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
Kobayashi et al., Cell 2002
(Salmonella Infections) :
Thus,
IRAK-M regulates
TLR signaling and innate immune homeostasis
Hazeki et al., Eur J Immunol 2003
:
PP2, an inhibitor of Src family tyrosine kinases, prevented the TLR induced phosphorylation of paxillin and Pyk2 without affecting
TLR induced
IRAK activation
Cuschieri et al., J Surg Res 2004
:
LPS stimulation led to the mobilization of
TLR4 to lipid rafts followed by phosphorylation and
activation of
IRAK , ERK 1/2, p38, and JNK/SAPK
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
Kubo-Murai et al., J Biochem 2008
:
Stimulation of these cells with
TLR ligands did not
cause the degradation of
IRAK-1 , which was clearly observed in the parent cells
Kawagoe et al., Nat Immunol 2008
:
Thus, IRAK2 is critical in late-phase
TLR responses , and
IRAK1 and IRAK2 are essential for the initial responses to TLR stimulation
Nguyen et al., Cell Signal 2009
:
Phosphorylation of
IRAK-1 by IRAK-4 in
response to
TLR activation may then release IRAK-1 from the inhibitory constraint exerted by its C-terminal domain
Cho et al., J Cell Physiol 2010
(Calcinosis) :
Overexpression of miR-146a induced the inhibition of
IRAK1 expression and inhibited basal and TNF-alpha- and
TLR ligand
induced osteogenic differentiation
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
Kumar Pachathundikandi et al., PloS one 2011
(Helicobacter Infections) :
Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces
IRAK-1 and I?B phosphorylation in a
TLR dependent manner, and this was required for activation of transcription factor NF-?B
Sandig et al., Eur J Immunol 2013
:
We show that while IRAK2 is redundant for TLR4 signaling,
IRAK1 is
essential for
TLR4 signaling in mast cells ... We show that while IRAK2 is redundant for TLR4 signaling,
IRAK1 is
essential for
TLR4 signaling in mast cells