Summary
Application
ELISA, IHC-P, WB
Basic Information
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Target
Full Name
TLR4 Toll Like Receptor 4
Alternative Names
ARMD10, CD284, hToll, TLR4, TOLL, toll like receptor 4
Function
Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195).
Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195,PubMed:21393102).
Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni2+. Responses triggered by Ni2+ require non-conserved histidines and are, therefore, species-specific (PubMed:20711192).
Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303).
In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL-) and mediates the cytokine release induced by LDL- (PubMed:23880187).
Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:9237759).
Activated by the signaling pathway regulator NMI which acts as damage-associated molecular patterns (DAMPs) in response to cell injury or pathogen invasion, therefore promoting nuclear factor NF-kappa-B activation (PubMed:29038465).
Biological Process
Biological Process activation of innate immune responseSource:Ensembl
Biological Process astrocyte developmentSource:Ensembl
Biological Process B cell proliferation involved in immune responseSource:Ensembl
Biological Process cellular response to amyloid-betaSource:ComplexPortal1 Publication
Biological Process cellular response to interferon-gammaSource:UniProtKB1 Publication
Biological Process cellular response to lipopolysaccharideSource:UniProtKB1 Publication
Biological Process cellular response to lipoteichoic acidSource:Ensembl
Biological Process cellular response to mechanical stimulusSource:UniProtKB1 Publication
Biological Process cellular response to oxidised low-density lipoprotein particle stimulusSource:ComplexPortal1 Publication
Biological Process cellular response to platelet-derived growth factor stimulusSource:Ensembl
Biological Process defense response to bacteriumSource:ARUK-UCL1 Publication
Biological Process defense response to Gram-negative bacteriumSource:GO_Central1 Publication
Biological Process detection of fungusSource:UniProtKB1 Publication
Biological Process detection of lipopolysaccharideSource:UniProtKB1 Publication
Biological Process ERK1 and ERK2 cascadeSource:Ensembl
Biological Process I-kappaB phosphorylationSource:BHF-UCL1 Publication
Biological Process immune responseSource:ProtInc1 Publication
Biological Process inflammatory responseSource:GO_Central1 Publication
Biological Process innate immune responseSource:BHF-UCL1 Publication
Biological Process intestinal epithelial structure maintenanceSource:BHF-UCL
Biological Process JNK cascadeSource:Ensembl
Biological Process lipopolysaccharide-mediated signaling pathwaySource:MGI2 Publications
Biological Process macrophage activationSource:UniProtKB1 Publication
Biological Process MHC class II biosynthetic processSource:Ensembl
Biological Process MyD88-dependent toll-like receptor signaling pathwaySource:ComplexPortal1 Publication
Biological Process negative regulation of cold-induced thermogenesisSource:YuBioLabBy Similarity
Biological Process negative regulation of ERK1 and ERK2 cascadeSource:BHF-UCL
Biological Process negative regulation of interferon-gamma productionSource:BHF-UCL
Biological Process negative regulation of interleukin-17 productionSource:BHF-UCL
Biological Process negative regulation of interleukin-23 productionSource:BHF-UCL
Biological Process negative regulation of interleukin-6 productionSource:BHF-UCL
Biological Process negative regulation of osteoclast differentiationSource:UniProtKB1 Publication
Biological Process negative regulation of tumor necrosis factor productionSource:BHF-UCL
Biological Process nitric oxide biosynthetic processSource:Ensembl
Biological Process nitric oxide production involved in inflammatory responseSource:Ensembl
Biological Process nucleotide-binding oligomerization domain containing 1 signaling pathwaySource:Ensembl
Biological Process nucleotide-binding oligomerization domain containing 2 signaling pathwaySource:Ensembl
Biological Process phagocytosisSource:UniProtKB1 Publication
Biological Process positive regulation of B cell proliferationSource:Ensembl
Biological Process positive regulation of cellular response to macrophage colony-stimulating factor stimulusSource:UniProtKB1 Publication
Biological Process positive regulation of chemokine (C-X-C motif) ligand 2 productionSource:ARUK-UCL1 Publication
Biological Process positive regulation of chemokine productionSource:BHF-UCL1 Publication
Biological Process positive regulation of cytokine production involved in inflammatory responseSource:ARUK-UCL1 Publication
Biological Process positive regulation of ERK1 and ERK2 cascadeSource:Ensembl
Biological Process positive regulation of gene expressionSource:UniProtKB1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingSource:Ensembl
Biological Process positive regulation of inflammatory responseSource:ARUK-UCL1 Publication
Biological Process positive regulation of interferon-alpha productionSource:BHF-UCL
Biological Process positive regulation of interferon-beta productionSource:BHF-UCL
Biological Process positive regulation of interferon-gamma productionSource:BHF-UCL
Biological Process positive regulation of interleukin-1 beta productionSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-1 productionSource:BHF-UCL
Biological Process positive regulation of interleukin-10 productionSource:BHF-UCL
Biological Process positive regulation of interleukin-12 productionSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-6 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-8 productionSource:UniProtKB1 Publication
Biological Process positive regulation of JNK cascadeSource:Ensembl
Biological Process positive regulation of macrophage activationSource:ARUK-UCL
Biological Process positive regulation of macrophage cytokine productionSource:Ensembl
Biological Process positive regulation of MAP kinase activitySource:BHF-UCL
Biological Process positive regulation of matrix metallopeptidase secretionSource:ARUK-UCL1 Publication
Biological Process positive regulation of MHC class II biosynthetic processSource:Ensembl
Biological Process positive regulation of NF-kappaB transcription factor activitySource:UniProtKB1 Publication
Biological Process positive regulation of NIK/NF-kappaB signalingSource:BHF-UCL1 Publication
Biological Process positive regulation of nitric oxide biosynthetic processSource:ARUK-UCL
Biological Process positive regulation of nitric-oxide synthase biosynthetic processSource:BHF-UCL
Biological Process positive regulation of NLRP3 inflammasome complex assemblySource:UniProtKB
Biological Process positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathwaySource:Ensembl
Biological Process positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathwaySource:Ensembl
Biological Process positive regulation of oxidative stress-induced neuron deathSource:ARUK-UCL
Biological Process positive regulation of platelet activationSource:BHF-UCLBy Similarity
Biological Process positive regulation of reactive oxygen species biosynthetic processSource:ARUK-UCL
Biological Process positive regulation of smooth muscle cell migrationSource:Ensembl
Biological Process positive regulation of smooth muscle cell proliferationSource:Ensembl
Biological Process positive regulation of transcription by RNA polymerase IISource:BHF-UCL
Biological Process positive regulation of tumor necrosis factor productionSource:UniProtKB1 Publication
Biological Process regulation of dendritic cell cytokine productionSource:Ensembl
Biological Process response to lipopolysaccharideSource:MGI2 Publications
Biological Process T-helper 1 type immune responseSource:UniProtKB1 Publication
Biological Process toll-like receptor 4 signaling pathwaySource:Ensembl
Biological Process toll-like receptor signaling pathwaySource:ComplexPortal1 Publication
Biological Process TRIF-dependent toll-like receptor signaling pathwaySource:ARUK-UCL
Biological Process wound healing involved in inflammatory responseSource:Ensembl
Cellular Location
Cell membrane
Early endosome
Cell projection, ruffle
Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis (PubMed:20037584).
Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation
Topology
Extracellular: 24-631
Helical: 632-652
Cytoplasmic: 653-839
PTM
N-glycosylated. Glycosylation of Asn-526 and Asn-575 seems to be necessary for the expression of TLR4 on the cell surface and the LPS-response. Likewise, mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS.
Phosphorylated on tyrosine residues by LYN after binding lipopolysaccharide.