KEGG   PATHWAY: ko04620Help
Entry
ko04620                     Pathway                                

Name
Toll-like receptor signaling pathway
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
ko04620  Toll-like receptor signaling pathway
ko04620

Ortholog table
Module
M00686  Toll-like receptor signaling [PATH:ko04620]
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
H00882  Cocoon syndrome
H01109  Chronic mucocutaneous candidiasis
H01502  Sjogren syndrome
Orthology
K05398  toll-like receptor 1
K10159  toll-like receptor 2
K10169  toll-like receptor 6
K05399  lipopolysaccharide-binding protein
K04391  monocyte differentiation antigen CD14
K05400  lymphocyte antigen 96
K05401  toll-like receptor 3
K10160  toll-like receptor 4
K10168  toll-like receptor 5
K05404  toll-like receptor 7
K10170  toll-like receptor 8
K01371  cathepsin K [EC:3.4.22.38]
K10161  toll-like receptor 9
K04392  Ras-related C3 botulinum toxin substrate 1
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K05402  toll-interacting protein
K04729  myeloid differentiation primary response protein MyD88
K05403  toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K02373  FAS-associated death domain protein
K04398  caspase 8 [EC:3.4.22.61]
K04733  interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04730  interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K03175  TNF receptor-associated factor 6 [EC:2.3.2.27]
K04403  TAK1-binding protein 1
K04404  TAK1-binding protein 2
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04415  mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04432  mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04430  mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04431  mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04448  transcription factor AP-1
K04379  proto-oncogene protein c-fos
K03156  tumor necrosis factor superfamily, member 2
K04519  interleukin 1 beta
K05405  interleukin 6
K05406  interleukin 12A
K05425  interleukin 12B
K10030  interleukin 8
K12499  C-C motif chemokine 5
K05408  C-C motif chemokine 3
K12964  C-C motif chemokine 4
K05409  TRIF-related adaptor molecule
K05842  toll-like receptor adapter molecule 1
K02861  receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K09446  interferon regulatory factor 5
K09447  interferon regulatory factor 7
K06250  secreted phosphoprotein 1
K07211  inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]
K05410  TANK-binding kinase 1 [EC:2.7.11.10]
K03174  TNF receptor-associated factor 3
K05411  interferon regulatory factor 3
K03160  tumor necrosis factor receptor superfamily member 5
K05412  CD80 antigen
K05413  CD86 antigen
K05414  interferon alpha
K05415  interferon beta
K05130  interferon receptor 1
K05131  interferon receptor 2
K11220  signal transducer and activator of transcription 1
K12671  C-X-C motif chemokine 10
K05416  C-X-C motif chemokine 9
K12672  C-X-C motif chemokine 11
Reference
  Authors
Kawai T, Akira S.
  Title
TLR signaling.
  Journal
Semin Immunol 19:24-32 (2007)
DOI:10.1016/j.smim.2006.12.004
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)
DOI:10.1038/nri2079
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)
DOI:10.1038/nri1900
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and Type I interferons.
  Journal
J Biol Chem 282:15319-23 (2007)
DOI:10.1074/jbc.R700009200
Reference
  Authors
Akira S, Uematsu S, Takeuchi O.
  Title
Pathogen recognition and innate immunity.
  Journal
Cell 124:783-801 (2006)
DOI:10.1016/j.cell.2006.02.015
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)
DOI:10.1016/j.molimm.2003.10.006
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)
DOI:10.4049/jimmunol.170.10.5165
Reference
  Authors
Aderem A, Smith KD.
  Title
A systems approach to dissecting immunity and inflammation.
  Journal
Semin Immunol 16:55-67 (2004)
DOI:10.1016/j.smim.2003.10.002
Reference
  Authors
Banerjee A, Gerondakis S.
  Title
Coordinating TLR-activated signaling pathways in cells of the immune system.
  Journal
Immunol Cell Biol 85:420-4 (2007)
DOI:10.1038/sj.icb.7100098
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)
DOI:10.1016/j.molimm.2007.04.002
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)
DOI:10.1038/82797
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and innate immunity.
  Journal
J Mol Med 84:712-25 (2006)
DOI:10.1007/s00109-006-0084-y

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