◀ Back to TLR4
TIRAP — TLR4
Pathways - manually collected, often from reviews:
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
-
NCI Pathway Database Endogenous TLR signaling:
IRAK2 (IRAK2)
→
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
-
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
-
NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
→
IRAK4 (IRAK4)
(modification, collaborate)
Park et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
-
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
-
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
-
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
-
NCI Pathway Database Endogenous TLR signaling:
HSP60/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HSPD1-MYD88-TIRAP)
→
HSP60/TLR4/MD2 (dimer) complex (TLR4-LY96-HSPD1)
(modification, collaborate)
Cohen-Sfady et al., J Immunol 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
HSP60/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HSPD1-MYD88-TIRAP)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Cohen-Sfady et al., J Immunol 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
HSP60/TLR4/MD2 (dimer) complex (TLR4-LY96-HSPD1)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Cohen-Sfady et al., J Immunol 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
MRP8/MRP14/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-MYD88-TIRAP-S100A8-S100A9)
→
MRP8/MRP14/TLR4/MD2 (dimer) complex (TLR4-LY96-S100A8-S100A9)
(modification, collaborate)
Vogl et al., Nat Med 2007
Evidence: assay
-
NCI Pathway Database Endogenous TLR signaling:
MRP8/MRP14/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-MYD88-TIRAP-S100A8-S100A9)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Vogl et al., Nat Med 2007
Evidence: assay
-
NCI Pathway Database Endogenous TLR signaling:
MRP8/MRP14/TLR4/MD2 (dimer) complex (TLR4-LY96-S100A8-S100A9)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Vogl et al., Nat Med 2007
Evidence: assay
-
NCI Pathway Database Endogenous TLR signaling:
BGN/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-BGN-MYD88-TIRAP)
→
BGN/TLR4/MD2 (dimer) complex (TLR4-LY96-BGN)
(modification, collaborate)
Schaefer et al., J Clin Invest 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
BGN/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-BGN-MYD88-TIRAP)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Schaefer et al., J Clin Invest 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
BGN/TLR4/MD2 (dimer) complex (TLR4-LY96-BGN)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Schaefer et al., J Clin Invest 2005
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
→
HMGB1/TLR4/MD2 (dimer) complex (TLR4-LY96-HMGB1)
(modification, collaborate)
Yu et al., Shock 2006
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer)/MYD88/TIRAP complex (TLR4-LY96-HMGB1-MYD88-TIRAP)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Yu et al., Shock 2006
Evidence: mutant phenotype
-
NCI Pathway Database Endogenous TLR signaling:
HMGB1/TLR4/MD2 (dimer) complex (TLR4-LY96-HMGB1)
→
MYD88/TIRAP complex (MYD88-TIRAP)
(modification, collaborate)
Yu et al., Shock 2006
Evidence: mutant phenotype
-
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
-
Reactome Reaction:
TIRAP
→
TLR4
(reaction)
Li et al., Proc Natl Acad Sci U S A 2002, Yamamoto et al., Nature 2002, Horng et al., Nature 2002, Jefferies et al., J Biol Chem 2003, Kollewe et al., J Biol Chem 2004, Gray et al., J Biol Chem 2006, Cheng et al., Biochem Biophys Res Commun 2007, Kawagoe et al., J Exp Med 2007, Núñez Miguel et al., PloS one 2007*, Piao et al., J Biol Chem 2008, Kawagoe et al., Nat Immunol 2008, Verstak et al., J Biol Chem 2009*
-
Reactome Reaction:
TIRAP
→
TLR4
(indirect_complex)
Yamamoto et al., Nature 2002, Horng et al., Nature 2002, Jefferies et al., J Biol Chem 2003, Brunner et al., Histol Histopathol 2005, Gray et al., J Biol Chem 2006, Núñez Miguel et al., PloS one 2007*, Piao et al., J Biol Chem 2008, Verstak et al., J Biol Chem 2009*, Lee et al., Proc Natl Acad Sci U S A 2012
-
WikiPathways TLR4 Signaling and Tolerance:
Complex of TIRAP-MAL-TRAM1-TLR4
→
TICAM1
(activation)
-
WikiPathways TLR4 Signaling and Tolerance:
Complex of TIRAP-MAL-TRAM1-TLR4
→
Complex of IRAK1-MYD88-IRAK4
(activation)
-
WikiPathways Toll-like Receptor Signaling:
TLR4
→
Complex of TIRAP-MYD88
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(physical association, affinity chromatography technology)
Horng et al., Nat Immunol 2001*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(direct interaction, pull down)
Horng et al., Nat Immunol 2001*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(physical association, affinity chromatography technology)
Fitzgerald et al., Nature 2001*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(direct interaction, protein complementation assay)
Ulrichts et al., FEBS Lett 2007*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(physical association, affinity chromatography technology)
Ulrichts et al., FEBS Lett 2007*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(direct interaction, protein complementation assay)
Ulrichts et al., Immunol Lett 2008*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(direct interaction, protein complementation assay)
Ulrichts et al., J Cell Sci 2010*
-
IRef Biogrid Interaction:
TLR4
—
TIRAP
(physical association, affinity chromatography technology)
Li et al., Immunity 2011
-
IRef Hprd Interaction:
TIRAP
—
TLR4
(in vivo)
Horng et al., Nat Immunol 2001*
-
IRef Intact Interaction:
Complex of 19 proteins
(association, anti tag coimmunoprecipitation)
Li et al., Immunity 2011
-
IRef Intact Interaction:
TLR4
—
TIRAP
(physical association, anti tag coimmunoprecipitation)
Fitzgerald et al., Nature 2001*
-
IRef Ophid Interaction:
TLR4
—
TIRAP
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
TLR4
—
TIRAP
(aggregation, confirmational text mining)
Horng et al., Nat Immunol 2001*
Text-mined interactions from Literome
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
Sacre et al., Am J Pathol 2007
(Arthritis, Rheumatoid...) :
Because TLR2 and
TLR4 require both MyD88 and
Mal/TIRAP for signaling, this study suggests that TLR function may regulate the expression of these factors in the RA synovium
Kagan et al., Nat Immunol 2008
:
We propose that
TLR4 first
induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes
Weller et al., Blood 2012
:
TLR4 and the TLR2 heterodimers ( with TLR1, TLR6, and possibly TLR10 )
require in addition the adaptor
TIRAP , whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9