Summary

Name TLR4
Full Name Toll-like receptor 4
Synonyms hToll
Primary ID O00206
Links - -
Type protein
Relations 24
Pathways FLT3-ITD signaling, Macrophage polarization, Monocyte: IL10 transcriptional regulation
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 Ni(2+). Responses triggered by Ni(2+) 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).

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Relations

Regulator Mechanism target score
+ up-regulates img/indirect-activation.png Immune_response 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png NfKb-p65/p50 0.564
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Macrophage polarization
+ up-regulates img/indirect-activation.png Interferon_Production 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TLR4 0.2
Publications: 1 Organism: Mus Musculus
Pathways:FLT3-ITD signaling, Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation JNK 0.508
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination TLR4 0.398
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png TLR4 0.396
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png JUN 0.462
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding TIRAP 0.772
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TIRAP 0.772
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Differentiation 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ERK1/2 0.445
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates activity img/indirect-activation.png MAP3K8 0.403
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png binding TICAM2 0.722
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/indirect-activation.png TLR4 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png binding TLR4 0.797
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK14 0.432
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates img/direct-activation.png binding TLR4 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Macrophage polarization
+ up-regulates activity img/direct-activation.png binding TICAM1 0.842
Publications: 1 Organism: Mus Musculus
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation p38 0.432
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TLR4 0.526
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png binding MYD88 0.757
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png binding TLR4 0.513
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png chemical activation TLR4 0.8
Publications: 1 Organism: Mus Musculus