Toll-like receptor signaling (Homo sapiens)

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1NucleusEndosomeCostimulatory moleculesAutocrine / ParacrineChemotactic effects(Neutrophil, immature DC,NK cell)T cell stimulation+p+pFlagellinUnmethylated CpG DNAAntiviral effectsProinflammatoryeffectsInflammatory cytokinesImidazoquinolinChemotactic effects (T cell)ssRNASpecific pathwayin pDCsdsRNAInflammatory cytokinesTLR2IFNA21IFNAR2AKT1IFNA8TNFTLR5MAPK3AKT3AKT2TLR7IFNA10TLR3IRAK1IL12BMAPK14Complement and coagulation cascadesIRF5FOSPeptidoglycan(Gram positive)IFNA7TOLLIPCD80TLR1TLR6IKBKETBK1IFNA16MyD88-dependent pathwayIRAK4CHUKTRAF3MYD88IFNB1PIK3R3RIPK1SPP1NFKB1MYD88MAPK9TIRAPFlagellar assemblyCCL4TRAF6IFNA2CD40IFNA14TICAM1IL12AIFNA13MAP2K2TLR9MAPK13Ubiquitin mediated proteolysisCD14IL8PIK3R5PIK3R1IRAK4TICAM2MyD88-independent pathwayIFNA5LPS (Gram negative)RAC1LY96MAP2K1ApoptosisMAPK1PIK3R2PIK3CBCASP8CCL5MAP3K8Zymosan (Yeast)CXCL11MYD88IFNB1TLR4PIK3CAMAPK12CCL3MAPK8IL1BCXCL9MYD88Lipoarabinomannans(Mycobacteria)LBPIFNA17MAPK10FADDMAP2K7CD86TLR2MAP3K7IFNA4IFNAR1IL6IRF7Cytokine-receptor interactionPIK3CGCXCL10TLR8IRAK1MAPK signaling pathwayIRF3TAB2Jak-STAT signaling pathwayIFNA1Lipoprotein particleTIRAPTRAF6MAP2K4PIK3CDIFNA6TAB1PI3K-Akt SignalingPathwayTRAF6STAT1MAPK11LipopolysaccharidebiosynthesisPPPPTAB3PPPPPPPPPPPIKBKGIKBKBPCHUKNFKB1RELANFKBIANFKBIBNFKBIAPNFKBIBPNFKBIANFKBIBPPJUNPPMAP2K3PMAP2K6P


Description

Toll-like receptors (TLRs) are a critical part of the innate immune response, and are expressed on macrophages and dendritic cells. TLRs are pattern-recognition receptors, and recognize molecules derived from microbes. Once activated, TLRs result in activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules

TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NFkB and MAPK; and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NFkB and MAPK.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

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Quality Tags

Ontology Terms

 

Bibliography

  1. Takeda K, Akira S; ''TLR signaling pathways.''; Semin Immunol, 2004 PubMed Europe PMC Scholia
  2. Kawai T, Akira S; ''Toll-like receptor and RIG-I-like receptor signaling.''; Ann N Y Acad Sci, 2008 PubMed Europe PMC Scholia
  3. ''KEGG Toll-like receptor signaling''; https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa04620,

History

View all...
CompareRevisionActionTimeUserComment
135009view11:27, 31 July 2024EweitzOntology Term : 'mast cell' added !
135008view11:26, 31 July 2024EweitzLabel cell types
135007view11:19, 31 July 2024EweitzOntology Term : 'dendritic cell' added !
135006view11:19, 31 July 2024EweitzOntology Term : 'macrophage' added !
135000view07:25, 31 July 2024EgonwAdded to articles
134999view03:49, 31 July 2024EweitzFix waypoint on segmented line
134998view03:36, 31 July 2024EweitzEconomize layout
134997view03:28, 31 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134996view03:27, 31 July 2024EweitzEconomize layout
134995view02:56, 31 July 2024EweitzCondense PI3K gene family
134994view02:25, 31 July 2024EweitzAvoid colliding interaction, enlarge font on overlooked node
134993view02:21, 31 July 2024EweitzFix membrane left
134992view02:19, 31 July 2024EweitzTweak positions of state icons; interaction anchors, line types
134991view02:07, 31 July 2024EweitzRefine alignment, line types, mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134990view02:01, 31 July 2024EweitzIncrease font size, for readability
134989view01:48, 31 July 2024EweitzEconomize layout
134988view01:22, 31 July 2024EweitzMove interaction nexus closer to interacting nodes
134987view01:19, 31 July 2024EweitzEconomize layout
134986view01:11, 31 July 2024EweitzAvoid stacking state indicators
134985view00:01, 31 July 2024EweitzRefine interactions
134984view23:58, 30 July 2024EweitzEconomize layout
134983view23:53, 30 July 2024EweitzTweak interaction waypoint
134982view23:51, 30 July 2024EweitzRefine interaction arrangement, economize layout
134981view23:48, 30 July 2024EweitzEconomize layout
134980view23:42, 30 July 2024EweitzEconomize layout
129709view01:30, 22 May 2024EweitzModified title
128034view17:21, 21 January 2024EweitzStack nodes, standardize case
127384view21:44, 26 September 2023Khanspersupdated phosphosites
119233view19:02, 22 June 2021Finterlyadded KEGG pathway info to publicationXref
118981view10:45, 6 June 2021EweitzUpdate WP619 title, straighten arrow
118980view10:40, 6 June 2021EweitzGroup clustered genes, connect interactions to it
117849view15:18, 22 May 2021EweitzModified title
111250view11:10, 27 July 2020EgonwMade a few more pathways clickable
105842view23:12, 15 August 2019KhanspersModified description
105228view07:41, 23 July 2019EgonwReplaced a secondary ChEBI identifiers with a primary identifier.
105219view00:12, 22 July 2019KhanspersModified description
105218view00:07, 22 July 2019Khanspersadded KEGG reference
105217view00:06, 22 July 2019KhanspersOntology Term : 'signaling pathway pertinent to immunity' added !
105216view00:04, 22 July 2019Khanspersadded phospho sites
105215view23:59, 21 July 2019Khanspersadded phospho sites
105214view23:44, 21 July 2019Khanspersupdate node size and layout
105213view23:19, 21 July 2019Khansperscleaned up MAPK
105212view22:56, 21 July 2019Khanspersupdated metabolites, added cellular components
102773view00:27, 24 January 2019AlexanderPicoremoved extra copy of IRAK4 and added TAB3
96020view15:22, 15 February 2018DeSlRemoved licence number
94908view23:52, 12 October 2017Khanspersconnected interactions
94760view15:49, 5 October 2017JmeliusConnect lines
83867view00:46, 18 December 2015AlexanderPicoModified title
72133view07:59, 25 October 2013Mkutmonadded datasource to pathway datanode
70634view09:40, 20 August 2013EgonwConverted a IUPAC-named Label into a Chemspider-backed Metabolite DataNode.

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProduct207 (Entrez Gene) Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
AKT2GeneProduct208 (Entrez Gene) Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
AKT3GeneProduct10000 (Entrez Gene) Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
ApoptosisPathwayWP254 (WikiPathways)
CASP8GeneProduct841 (Entrez Gene) Original kegg element: gene;87;hsa:841
CCL3GeneProduct6348 (Entrez Gene) Original kegg element: gene;44;hsa:6348
CCL4GeneProduct6351 (Entrez Gene) Original kegg element: gene;38;hsa:6351
CCL5GeneProduct6352 (Entrez Gene) Original kegg element: gene;58;hsa:6352
CD14GeneProduct929 (Entrez Gene) Original kegg element: gene;84;hsa:929
CD40GeneProduct958 (Entrez Gene) Original kegg element: gene;29;hsa:958
CD80GeneProduct941 (Entrez Gene) Original kegg element: gene;69;hsa:941
CD86GeneProduct942 (Entrez Gene) Original kegg element: gene;28;hsa:942
CHUKGeneProduct1147 (Entrez Gene) Original kegg element: gene;2;hsa:1147
CHUKGeneProductENSG00000213341 (Ensembl)
CXCL10GeneProduct3627 (Entrez Gene) Original kegg element: gene;25;hsa:3627
CXCL11GeneProduct6373 (Entrez Gene) Original kegg element: gene;23;hsa:6373
CXCL9GeneProduct4283 (Entrez Gene) Original kegg element: gene;24;hsa:4283
Complement and coagulation cascadesPathwayWP558 (WikiPathways)
Cytokine-receptor interactionPathwayWP530 (WikiPathways)
FADDGeneProduct8772 (Entrez Gene) Original kegg element: gene;56;hsa:8772
FOSGeneProduct2353 (Entrez Gene) Original kegg element: gene;35;hsa:2353 hsa:3725
Flagellar assemblyPathway
IFNA10GeneProduct3446 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA13GeneProduct3447 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA1GeneProduct3439 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA14GeneProduct3448 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA16GeneProduct3449 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA17GeneProduct3451 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA21GeneProduct3452 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA2GeneProduct3440 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA4GeneProduct3441 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA5GeneProduct3442 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA6GeneProduct3443 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA7GeneProduct3444 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA8GeneProduct3445 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNAR1GeneProduct3454 (Entrez Gene) Original kegg element: gene;49;hsa:3454 hsa:3455
IFNAR2GeneProduct3455 (Entrez Gene) Original kegg element: gene;49;hsa:3454 hsa:3455
IFNB1GeneProduct3456 (Entrez Gene) Original kegg element: gene;1;hsa:3456
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKEGeneProduct9641 (Entrez Gene) Original kegg element: gene;54;hsa:9641
IKBKGGeneProductENSG00000269335 (Ensembl)
IL12AGeneProduct3592 (Entrez Gene) Original kegg element: gene;45;hsa:3592 hsa:3593
IL12BGeneProduct3593 (Entrez Gene) Original kegg element: gene;45;hsa:3592 hsa:3593
IL1BGeneProduct3553 (Entrez Gene) Original kegg element: gene;51;hsa:3553
IL6GeneProduct3569 (Entrez Gene) Original kegg element: gene;57;hsa:3569
IL8GeneProduct3576 (Entrez Gene) Original kegg element: gene;43;hsa:3576
IRAK1GeneProduct3654 (Entrez Gene) Original kegg element: gene;41;hsa:3654
IRAK4GeneProduct51135 (Entrez Gene) Original kegg element: gene;86;hsa:51135
IRF3GeneProduct3661 (Entrez Gene) Original kegg element: gene;67;hsa:3661
IRF5GeneProduct3663 (Entrez Gene) Original kegg element: gene;21;hsa:3663
IRF7GeneProduct3665 (Entrez Gene) Original kegg element: gene;20;hsa:3665
ImidazoquinolinMetabolite14697812 (Chemspider)
JUNGeneProduct3725 (Entrez Gene)
Jak-STAT signaling pathwayPathwayWP619 (WikiPathways)
LBPGeneProduct3929 (Entrez Gene) Original kegg element: gene;77;hsa:3929
LPS (Gram negative)MetaboliteCHEBI:52603 (ChEBI)
LY96GeneProduct23643 (Entrez Gene) Original kegg element: gene;71;hsa:23643
Lipoarabinomannans (Mycobacteria)MetaboliteCHEBI:59524 (ChEBI)
Lipopolysaccharide biosynthesisPathway
Lipoprotein particleMetaboliteCHEBI:6495 (ChEBI)
MAP2K1GeneProduct5604 (Entrez Gene) Original kegg element: gene;12;hsa:5604 hsa:5605
MAP2K2GeneProduct5605 (Entrez Gene) Original kegg element: gene;12;hsa:5604 hsa:5605
MAP2K3GeneProduct5606 (Entrez Gene)
MAP2K4GeneProduct6416 (Entrez Gene) Original kegg element: gene;63;hsa:5609 hsa:6416
MAP2K6GeneProduct5608 (Entrez Gene)
MAP2K7GeneProduct5609 (Entrez Gene) Original kegg element: gene;63;hsa:5609 hsa:6416
MAP3K7GeneProduct6885 (Entrez Gene) Original kegg element: gene;37;hsa:6885
MAP3K8GeneProduct1326 (Entrez Gene) Original kegg element: gene;13;hsa:1326
MAPK signaling pathwayPathwayWP382 (WikiPathways)
MAPK10GeneProduct5602 (Entrez Gene) Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
MAPK11GeneProduct5600 (Entrez Gene) Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
MAPK12GeneProduct6300 (Entrez Gene) Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
MAPK13GeneProduct5603 (Entrez Gene) Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
MAPK14GeneProduct1432 (Entrez Gene) Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
MAPK1GeneProduct5594 (Entrez Gene) Original kegg element: gene;11;hsa:5594 hsa:5595
MAPK3GeneProduct5595 (Entrez Gene) Original kegg element: gene;11;hsa:5594 hsa:5595
MAPK8GeneProduct5599 (Entrez Gene) Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
MAPK9GeneProduct5601 (Entrez Gene) Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
MYD88GeneProduct4615 (Entrez Gene) Original kegg element: gene;47;hsa:4615
MyD88-dependent pathwayPathway
MyD88-independent pathwayPathway
NFKB1GeneProduct4790 (Entrez Gene)
NFKBIAGeneProductENSG00000100906 (Ensembl)
NFKBIBGeneProductENSG00000104825 (Ensembl)
PI3K-Akt Signaling PathwayPathwayWP4172 (WikiPathways)
PIK3CAGeneProduct5290 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3CBGeneProduct5291 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3CDGeneProduct5293 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3CGGeneProduct5294 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3R1GeneProduct5295 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3R2GeneProduct5296 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3R3GeneProduct8503 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
PIK3R5GeneProduct23533 (Entrez Gene) Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
Peptidoglycan (Gram positive)MetaboliteCHEBI:8005 (ChEBI)
RAC1GeneProduct5879 (Entrez Gene) Original kegg element: gene;48;hsa:5879
RELAGeneProductENSG00000173039 (Ensembl)
RIPK1GeneProduct8737 (Entrez Gene) Original kegg element: gene;17;hsa:8737
SPP1GeneProduct6696 (Entrez Gene) Original kegg element: gene;15;hsa:6696
STAT1GeneProduct6772 (Entrez Gene) Original kegg element: gene;62;hsa:6772
TAB1GeneProduct10454 (Entrez Gene) Original kegg element: gene;59;hsa:10454
TAB2GeneProduct23118 (Entrez Gene) Original kegg element: gene;61;hsa:23118
TAB3GeneProduct257397 (Entrez Gene) Original kegg element: gene;61;hsa:23118
TBK1GeneProduct29110 (Entrez Gene) Original kegg element: gene;52;hsa:29110
TICAM1GeneProduct148022 (Entrez Gene) Original kegg element: gene;82;hsa:148022
TICAM2GeneProduct353376 (Entrez Gene) Original kegg element: gene;80;hsa:353376
TIRAPGeneProduct114609 (Entrez Gene) Original kegg element: gene;46;hsa:114609
TLR1GeneProduct7096 (Entrez Gene) Original kegg element: gene;75;hsa:7096
TLR2GeneProduct7097 (Entrez Gene) Original kegg element: gene;74;hsa:7097
TLR3GeneProduct7098 (Entrez Gene) Original kegg element: gene;73;hsa:7098
TLR4GeneProduct7099 (Entrez Gene) Original kegg element: gene;79;hsa:7099
TLR5GeneProduct7100 (Entrez Gene) Original kegg element: gene;72;hsa:7100
TLR6GeneProduct10333 (Entrez Gene) Original kegg element: gene;76;hsa:10333
TLR7GeneProduct51284 (Entrez Gene) Original kegg element: gene;39;hsa:51284 hsa:51311
TLR8GeneProduct51311 (Entrez Gene) Original kegg element: gene;39;hsa:51284 hsa:51311
TLR9GeneProduct54106 (Entrez Gene) Original kegg element: gene;78;hsa:54106
TNFGeneProduct7124 (Entrez Gene) Original kegg element: gene;66;hsa:7124
TOLLIPGeneProduct54472 (Entrez Gene) Original kegg element: gene;81;hsa:54472
TRAF3GeneProduct7187 (Entrez Gene) Original kegg element: gene;16;hsa:7187
TRAF6GeneProduct7189 (Entrez Gene) Original kegg element: gene;9;hsa:7189
Ubiquitin mediated proteolysisPathway
Zymosan (Yeast)MetaboliteCHEBI:37671 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP75"
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