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
Toll-like receptor signaling pathway
ko04620

All organismsOrtholog 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
H00821  
Macular degeneration
H00882  
Cocoon syndrome
H01109  
Chronic mucocutaneous candidiasis (CMC)
Orthology
K05398  
toll-like receptor 1
K10159  
toll-like receptor 2
K10169  
toll-like receptor 6
K05399  
lipopolysaccharide-binding protein
K04391  
CD14 antigen
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 [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase, regulatory subunit
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
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  
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)
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)

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