KEGG   PATHWAY: hsa04620Help
hsa04620                    Pathway                                

Toll-like receptor signaling pathway - Homo sapiens (human)
Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid 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 NF-{kappa}B 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 NF-{kappa}B and MAPK.
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
hsa04620  Toll-like receptor signaling pathway

Ortholog table
nt06121  TLR signaling (virus)
nt06122  IFN signaling (virus)
nt06161  Human immunodeficiency virus type 1 (HIV-1)
nt06162  Hepatitis B virus (HBV)
nt06163  Hepatitis C virus (HCV)
nt06164  Kaposi sarcoma-associated herpesvirus (KSHV)
nt06165  Epstein-Barr virus (EBV)
nt06166  Human papillomavirus (HPV)
nt06168  Herpes simplex virus 1 (HSV-1)
nt06169  Measles virus (MV)
nt06170  Influenza A virus (IAV)
nt06221  TLR signaling
nt06222  IFN signaling
nt06263  Hepatocellular carcinoma
N00148  TLR3-IRF7 signaling pathway
N00149  TLR3-IRF3 signaling pathway
N00150  Type I IFN signaling pathway
N00435  TLR2/4-NFKB signaling pathway
N00438  TLR2/4-MAPK signaling pathway
N00553  TLR4-IRF3/7 signaling pathway
N00563  TLR3-NFKB signaling pathway
N00690  TLR7/9-IRF7 signaling pathway
H00096  Defects of toll-like receptor signaling
H00273  Pycnodysostosis
H00344  Leprosy
H00425  Lysosomal cysteine protease deficiencies
H00721  Pyogenic bacterial infections, recurrent, due to MYD88 deficiency
H00882  Cocoon syndrome
H01109  Chronic mucocutaneous candidiasis
H01502  Sjogren syndrome
D00745  Interferon alfa-2a (USAN/INN)
D00746  Interferon beta-1b (USAN/INN)
D02500  Imiquimod (JAN/USAN/INN)
D02744  Interferon alfacon-1 (USAN/INN)
D02745  Interferon alfa-2b (USAN)
D02747  Peginterferon alfa-2a (USAN/INN)
D02748  Peginterferon alfa-2b (INN)
D03304  Interferon beta (JAN)
D03305  Interferon alfa (NAMALWA) (JP17)
D03441  Certolizumab pegol (USAN/INN)
D04043  Eritoran tetrasodium (USAN)
D04295  Galiximab (USAN/INN)
D04552  Interferon alfa-n1 (USAN)
D04553  Interferon alfa-n3 (USAN)
D04554  Interferon beta-1a (USAN)
D04619  Isatoribine (USAN)
D04787  Loxoribine (USAN/INN)
D06071  Teneliximab (USAN/INN)
D06619  Mifamurtide (USAN)
D06634  Relacatib (USAN/INN)
D06635  Rilonacept (USAN/INN)
D08841  Agatolimod (USAN)
D08842  Agatolimod sodium (USAN)
D08844  Albinterferon alfa-2b (USAN)
D08955  Odanacatib (JAN/USAN)
D09573  Eritoran sodium (JAN)
D09639  Losmapimod (USAN/INN)
D09661  Rintatolimod (USAN/INN)
D10483  Peginterferon beta-1a (USAN/INN)
D11003  Vesatolimod (USAN/INN)
D11027  Ropeginterferon alfa-2b (INN)
D11357  Bleselumab (USAN)
D11491  Selicrelumab (USAN/INN)
D11503  Tomaralimab (USAN)
D11504  Tilsotolimod (USAN/INN)
D11505  Tilsotolimod sodium (USAN)
Homo sapiens (human) [GN:hsa]
7096  TLR1; toll like receptor 1 [KO:K05398]
7097  TLR2; toll like receptor 2 [KO:K10159]
10333  TLR6; toll like receptor 6 [KO:K10169]
3929  LBP; lipopolysaccharide binding protein [KO:K05399]
929  CD14; CD14 molecule [KO:K04391]
23643  LY96; lymphocyte antigen 96 [KO:K05400]
7098  TLR3; toll like receptor 3 [KO:K05401]
7099  TLR4; toll like receptor 4 [KO:K10160]
7100  TLR5; toll like receptor 5 [KO:K10168]
51284  TLR7; toll like receptor 7 [KO:K05404]
51311  TLR8; toll like receptor 8 [KO:K10170]
1513  CTSK; cathepsin K [KO:K01371] [EC:]
54106  TLR9; toll like receptor 9 [KO:K10161]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
54472  TOLLIP; toll interacting protein [KO:K05402]
4615  MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]
114609  TIRAP; TIR domain containing adaptor protein [KO:K05403]
8772  FADD; Fas associated via death domain [KO:K02373]
841  CASP8; caspase 8 [KO:K04398] [EC:]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:]
3654  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:]
10454  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
23118  TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
1326  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
5606  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:]
5608  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:]
6416  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
7124  TNF; tumor necrosis factor [KO:K03156]
3553  IL1B; interleukin 1 beta [KO:K04519]
3569  IL6; interleukin 6 [KO:K05405]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
6348  CCL3; C-C motif chemokine ligand 3 [KO:K05408]
6349  CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]
414062  CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]
6351  CCL4; C-C motif chemokine ligand 4 [KO:K12964]
9560  CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964]
388372  CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964]
353376  TICAM2; toll like receptor adaptor molecule 2 [KO:K05409]
148022  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
8737  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:]
3663  IRF5; interferon regulatory factor 5 [KO:K09446]
3665  IRF7; interferon regulatory factor 7 [KO:K09447]
6696  SPP1; secreted phosphoprotein 1 [KO:K06250]
9641  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:]
7187  TRAF3; TNF receptor associated factor 3 [KO:K03174]
3661  IRF3; interferon regulatory factor 3 [KO:K05411]
958  CD40; CD40 molecule [KO:K03160]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
3439  IFNA1; interferon alpha 1 [KO:K05414]
3440  IFNA2; interferon alpha 2 [KO:K05414]
3441  IFNA4; interferon alpha 4 [KO:K05414]
3442  IFNA5; interferon alpha 5 [KO:K05414]
3443  IFNA6; interferon alpha 6 [KO:K05414]
3444  IFNA7; interferon alpha 7 [KO:K05414]
3445  IFNA8; interferon alpha 8 [KO:K05414]
3446  IFNA10; interferon alpha 10 [KO:K05414]
3447  IFNA13; interferon alpha 13 [KO:K05414]
3448  IFNA14; interferon alpha 14 [KO:K05414]
3449  IFNA16; interferon alpha 16 [KO:K05414]
3451  IFNA17; interferon alpha 17 [KO:K05414]
3452  IFNA21; interferon alpha 21 [KO:K05414]
3456  IFNB1; interferon beta 1 [KO:K05415]
3454  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
3455  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
6772  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
3627  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
4283  CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]
6373  CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]
Kawai T, Akira S.
TLR signaling.
Semin Immunol 19:24-32 (2007)
O'Neill LA, Bowie AG.
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
Nat Rev Immunol 7:353-64 (2007)
Honda K, Taniguchi T.
IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
Nat Rev Immunol 6:644-58 (2006)
Uematsu S, Akira S.
Toll-like receptors and Type I interferons.
J Biol Chem 282:15319-23 (2007)
Akira S, Uematsu S, Takeuchi O.
Pathogen recognition and innate immunity.
Cell 124:783-801 (2006)
Yamamoto M, Takeda K, Akira S.
TIR domain-containing adaptors define the specificity of TLR signaling.
Mol Immunol 40:861-8 (2004)
Means TK, Hayashi F, Smith KD, Aderem A, Luster AD.
The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells.
J Immunol 170:5165-75 (2003)
Aderem A, Smith KD.
A systems approach to dissecting immunity and inflammation.
Semin Immunol 16:55-67 (2004)
Banerjee A, Gerondakis S.
Coordinating TLR-activated signaling pathways in cells of the immune system.
Immunol Cell Biol 85:420-4 (2007)
Loniewski KJ, Patial S, Parameswaran N.
Sensitivity of TLR4- and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF-receptor-associated-factor-6 revealed by RNAi in mouse macrophages.
Mol Immunol 44:3715-23 (2007)
Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG.
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
Nat Immunol 1:533-40 (2000)
Uematsu S, Akira S.
Toll-like receptors and innate immunity.
J Mol Med 84:712-25 (2006)
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