TLR4 signaling and tolerance (WP3851)

Homo sapiens

This pathway is based on the figure 2 of "Toll-like Receptors: Novel Pharmacological Targets for the Treatment of Neurological Diseases" and figure 2 of "Toll-like receptor and its roles in myocardial ischemic/reperfusion injury" (see bibliography). The Toll-like receptors are used by mammals to recognize pathogen-associated molecules such as the cell wall components. The activation of TLR4 causes a cell's inability to produce TNFa. TLR4 deals with MyD88 independent and dependent pathways, and due to LPS tolerant cells, inhibitors of the MyD88 dependent pathway are increased. TLR is important in the creation of protective immune responses to cancers, and the protection of brain tissue from injury. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal].


AAR&Co , Martina Summer-Kutmon , Kristina Hanspers , Egon Willighagen , Alex Pico , and Eric Weitz


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Homo sapiens



Pathway Ontology

regulatory pathway neurological disorder pathway


Label Type Compact URI Comment
Ikki GeneProduct uniprot:Q14164
TNF GeneProduct uniprot:P01375
TIRAP GeneProduct ensembl:ENSG00000150455
IRF3 GeneProduct ensembl:ENSG00000126456
IRAK1 GeneProduct ensembl:ENSG00000184216
MAL GeneProduct uniprot:P58753
IRAK-M GeneProduct uniprot:Q9Y616
TRAF6 GeneProduct ensembl:ENSG00000175104
IKKa GeneProduct uniprot:O15111
TRIF GeneProduct uniprot:Q8IUC6
TAK1 GeneProduct uniprot:O43318
MYD88 GeneProduct ensembl:ENSG00000172936
IKKb GeneProduct uniprot:O14920
TRAF3 GeneProduct ensembl:ENSG00000131323
NFKB1 GeneProduct ensembl:ENSG00000109320 NFKB not specified
TBK1 GeneProduct ensembl:ENSG00000183735
NAP1 GeneProduct uniprot:P10145
RIP1 GeneProduct uniprot:Q13546
IFNB GeneProduct ensembl:ENSG00000171855
TAB2 GeneProduct ensembl:ENSG00000055208
TRAM GeneProduct ensembl:ENSG00000067167 TRAM not specified
TLR4 GeneProduct ensembl:ENSG00000136869
NEMO GeneProduct uniprot:Q9Y6K9
TAB1 GeneProduct ensembl:ENSG00000100324
IL6 GeneProduct ensembl:ENSG00000136244
SHIP1 GeneProduct uniprot:Q92835
IRAK4 GeneProduct ensembl:ENSG00000198001
IkBa GeneProduct uniprot:P25963
IRF3 GeneProduct ensembl:ENSG00000126456
NFKB1 GeneProduct ensembl:ENSG00000109320 NFKB not specified
IRF7 GeneProduct ensembl:ENSG00000185507
IRF7 GeneProduct ensembl:ENSG00000185507


  1. Toll-like receptors: novel pharmacological targets for the treatment of neurological diseases. Marsh BJ, Stenzel-Poore MP. Curr Opin Pharmacol. 2008 Feb;8(1):8–13. PubMed Europe PMC Scholia
  2. Toll-like receptor and its roles in myocardial ischemic/reperfusion injury. Fang Y, Hu J. Med Sci Monit. 2011 Apr;17(4):RA100-9. PubMed Europe PMC Scholia