KEGG   PATHWAY: hsa04620Help
Entry
hsa04620                    Pathway                                

Name
Toll-like receptor signaling pathway - Homo sapiens (human)
Description
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.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
Toll-like receptor signaling pathway
hsa04620

All organismsOrtholog table
Disease
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
H00821  
Macular degeneration
H00882  
Cocoon syndrome
H01109  
Chronic mucocutaneous candidiasis (CMC)
Drug
D00745  
Interferon alfa-2a (genetical recombination) (JAN)
D00746  
Interferon beta-1b (genetical recombination) (JAN)
D02500  
Imiquimod (JAN/USAN/INN)
D02744  
Interferon alfacon-1 (genetical recombination) (JAN)
D02745  
Interferon alfa-2b (genetical recombination) (JAN)
D02747  
Peginterferon alfa-2a (genetical recombination) (JAN)
D02748  
Peginterferon alfa-2b (generical recombination) (JAN)
D03203  
Abatacept (genetical recombination) (JAN)
D03304  
Interferon beta (JAN)
D03305  
Interferon alfa (BALL-1) (JAN)
D03441  
Certolizumab pegol (genetical recombination) (JAN)
D04043  
Eritoran tetrasodium (USAN)
D04295  
Galiximab (USAN/INN)
D04552  
Interferon alfa-n1 (USAN)
D04554  
Interferon beta-1a (genetical recombination) (JAN)
D04619  
Isatoribine (USAN)
D04787  
Loxoribine (USAN/INN)
D06071  
Teneliximab (USAN/INN)
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)
Organism
Homo sapiens (human) [GN:hsa]
Gene
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:3.4.22.38]
54106  
TLR9; toll-like receptor 9 [KO:K10161]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
54472  
TOLLIP; toll interacting protein [KO:K05402]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
114609  
TIRAP; toll-interleukin 1 receptor (TIR) domain containing adaptor protein [KO:K05403]
8772  
FADD; Fas (TNFRSF6)-associated via death domain [KO:K02373]
841  
CASP8; caspase 8, apoptosis-related cysteine peptidase [KO:K04398] [EC:3.4.22.61]
51135  
IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3654  
IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
7189  
TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
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:2.7.11.25]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
1326  
MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5606  
MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
5608  
MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
6416  
MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
5609  
MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  
JUN; jun proto-oncogene [KO:K04448]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [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; chemokine (C-X-C motif) ligand 8 [KO:K10030]
6352  
CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
6348  
CCL3; chemokine (C-C motif) ligand 3 [KO:K05408]
6349  
CCL3L1; chemokine (C-C motif) ligand 3-like 1 [KO:K05408]
414062  
CCL3L3; chemokine (C-C motif) ligand 3-like 3 [KO:K05408]
6351  
CCL4; chemokine (C-C motif) ligand 4 [KO:K12964]
9560  
CCL4L2; chemokine (C-C motif) ligand 4-like 2 [KO:K12964]
388372  
CCL4L1; chemokine (C-C motif) 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 (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
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 kappa light polypeptide gene enhancer in B-cells, kinase epsilon [KO:K07211] [EC:2.7.11.10]
29110  
TBK1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
7187  
TRAF3; TNF receptor-associated factor 3 [KO:K03174]
3661  
IRF3; interferon regulatory factor 3 [KO:K05411]
958  
CD40; CD40 molecule, TNF receptor superfamily member 5 [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, fibroblast [KO:K05415]
3454  
IFNAR1; interferon (alpha, beta and omega) receptor 1 [KO:K05130]
3455  
IFNAR2; interferon (alpha, beta and omega) receptor 2 [KO:K05131]
6772  
STAT1; signal transducer and activator of transcription 1, 91kDa [KO:K11220]
3627  
CXCL10; chemokine (C-X-C motif) ligand 10 [KO:K12671]
4283  
CXCL9; chemokine (C-X-C motif) ligand 9 [KO:K05416]
6373  
CXCL11; chemokine (C-X-C motif) ligand 11 [KO:K12672]
Reference
  Authors
Kawai T, Akira S.
  Title
TLR signaling.
  Journal
Semin Immunol 19:24-32 (2007)
Reference
  Authors
O'Neill LA, Bowie AG.
  Title
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
  Journal
Nat Rev Immunol 7:353-64 (2007)
Reference
  Authors
Honda K, Taniguchi T.
  Title
IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
  Journal
Nat Rev Immunol 6:644-58 (2006)
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and Type I interferons.
  Journal
J Biol Chem 282:15319-23 (2007)
Reference
  Authors
Akira S, Uematsu S, Takeuchi O.
  Title
Pathogen recognition and innate immunity.
  Journal
Cell 124:783-801 (2006)
Reference
  Authors
Yamamoto M, Takeda K, Akira S.
  Title
TIR domain-containing adaptors define the specificity of TLR signaling.
  Journal
Mol Immunol 40:861-8 (2004)
Reference
  Authors
Matsumoto M, Oshiumi H, Seya T.
  Title
[TICAM-1, an adaptor molecule that participates in Toll-like receptor-mediated type1 interferon production.] (In Japanese)
  Journal
Molecular Medicine 40:194-200 (2003)
Reference
  Authors
Means TK, Hayashi F, Smith KD, Aderem A, Luster AD.
  Title
The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells.
  Journal
J Immunol 170:5165-75 (2003)
Reference
  Authors
Aderem A, Smith KD.
  Title
A systems approach to dissecting immunity and inflammation.
  Journal
Semin Immunol 16:55-67 (2004)
Reference
  Authors
Banerjee A, Gerondakis S.
  Title
Coordinating TLR-activated signaling pathways in cells of the immune system.
  Journal
Immunol Cell Biol : (2007)
Reference
  Authors
Loniewski KJ, Patial S, Parameswaran N.
  Title
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.
  Journal
Mol Immunol 44:3715-23 (2007)
Reference
  Authors
Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG.
  Title
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
  Journal
Nat Immunol 1:533-40 (2000)
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and innate immunity.
  Journal
J Mol Med 84:712-25 (2006)
KO pathway
 

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