TLR4 signaling and tolerance (WP3851)
Homo sapiens
Toll-like receptors (TLRs) are used by mammals to recognize pathogen-associated molecules such as cell wall components. TLR4 activation inhibits a cell’s ability to produce TNFa. TLR4 deals with MyD88 independent and dependent pathways. Due to LPS-tolerant cells, inhibitors of the MyD88 dependent pathway are increased. TLRs are important in immune responses to cancers, and protecting brain tissue from injury. 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). Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.
Authors
AAR&Co , Martina Summer-Kutmon , Kristina Hanspers , Egon Willighagen , Alex Pico , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
regulatory pathway neurological disorder pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| TRIF | GeneProduct | uniprot:Q8IUC6 | |
| RIP1 | GeneProduct | uniprot:Q13546 | |
| NAP1 | GeneProduct | uniprot:P10145 | |
| MAL | GeneProduct | uniprot:P58753 | |
| IRAK3 | GeneProduct | uniprot:Q9Y616 | 'IRAK-M' originally |
| IKBKE | GeneProduct | uniprot:Q14164 | 'Ikki' originally |
| IL6 | GeneProduct | ensembl:ENSG00000136244 | |
| TRAM | GeneProduct | ensembl:ENSG00000067167 | TRAM not specified |
| IRF3 | GeneProduct | ensembl:ENSG00000126456 | |
| TAB1 | GeneProduct | ensembl:ENSG00000100324 | |
| TLR4 | GeneProduct | ensembl:ENSG00000136869 | |
| NEMO | GeneProduct | uniprot:Q9Y6K9 | |
| TBK1 | GeneProduct | ensembl:ENSG00000183735 | |
| TNF | GeneProduct | uniprot:P01375 | |
| MYD88 | GeneProduct | ensembl:ENSG00000172936 | |
| IFNB | GeneProduct | ensembl:ENSG00000171855 | |
| CHUK | GeneProduct | uniprot:O15111 | 'IKKa' originally |
| SHIP1 | GeneProduct | uniprot:Q92835 | |
| TAK1 | GeneProduct | uniprot:O43318 | |
| TIRAP | GeneProduct | ensembl:ENSG00000150455 | |
| TAB2 | GeneProduct | ensembl:ENSG00000055208 | |
| IKBKB | GeneProduct | uniprot:O14920 | 'IKKb' originally |
| IkBa | GeneProduct | uniprot:P25963 | |
| IRAK1 | GeneProduct | ensembl:ENSG00000184216 | |
| IRAK4 | GeneProduct | ensembl:ENSG00000198001 | |
| NFKB1 | GeneProduct | ensembl:ENSG00000109320 | NFKB not specified |
| TRAF3 | GeneProduct | ensembl:ENSG00000131323 | |
| TRAF6 | GeneProduct | ensembl:ENSG00000175104 | |
| IRF7 | GeneProduct | ensembl:ENSG00000185507 |
References
- 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
- 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