KEGG   PATHWAY: tru04620
Entry
tru04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Takifugu rubripes (torafugu)
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
Pathway map
tru04620  Toll-like receptor signaling pathway
tru04620

Organism
Takifugu rubripes (torafugu) [GN:tru]
Gene
100134852  ticam; toll-like receptor adaptor molecule [KO:K05842]
100134853  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
100134854  tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
100271746  cd40; CD40 antigen precursor [KO:K03160]
101061322  [KO:K04398] [EC:3.4.22.61]
101061527  [KO:K02649]
101061662  tlr3; toll-like receptor 3 [KO:K05401]
101061773  irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
101061955  [KO:K05406]
101062431  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101062512  [KO:K02649]
101062562  [KO:K10168]
101062695  [KO:K04441] [EC:2.7.11.24]
101062734  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
101063410  rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101063524  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101063584  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101063692  [KO:K02649]
101063834  [KO:K05399]
101063878  irf9; interferon regulatory factor 9 [KO:K04693]
101064045  [KO:K04441] [EC:2.7.11.24]
101064151  [KO:K04430] [EC:2.7.12.2]
101064650  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101064673  [KO:K04433] [EC:2.7.12.2]
101064726  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
101064747  [KO:K05414]
101064806  jun; transcription factor AP-1 [KO:K04448]
101065036  [KO:K12964]
101065244  [KO:K02649]
101065438  [KO:K04456] [EC:2.7.11.1]
101066166  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101066261  [KO:K01371] [EC:3.4.22.38]
101066430  irak4; interleukin-1 receptor-associated kinase 4 isoform X2 [KO:K04733] [EC:2.7.11.1]
101066563  [KO:K04371] [EC:2.7.11.24]
101066893  tlr5; toll-like receptor 5 [KO:K10168]
101066952  [KO:K05425]
101067067  [KO:K02373]
101067160  [KO:K04392]
101067191  [KO:K00922] [EC:2.7.1.153]
101067377  [KO:K04441] [EC:2.7.11.24]
101067832  [KO:K04379]
101067839  mapk10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
101068225  [KO:K04467] [EC:2.7.11.10]
101068404  [KO:K04379]
101068527  [KO:K10159]
101068557  tlr2; toll-like receptor 2 [KO:K10159]
101068711  [KO:K04734]
101068715  [KO:K04441] [EC:2.7.11.24]
101068828  stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101068840  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101069060  irf7; interferon regulatory factor 7 [KO:K09447]
101069247  map3k8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
101069621  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
101069645  [KO:K07210]
101069880  [KO:K04467] [EC:2.7.11.10]
101069888  traf3; TNF receptor-associated factor 3 [KO:K03174]
101069931  irf5; interferon regulatory factor 5 isoform X1 [KO:K09446]
101070190  [KO:K04440] [EC:2.7.11.24]
101070236  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101070421  cxcl11; C-X-C motif chemokine 11 [KO:K05416]
101071013  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101071368  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101071462  [KO:K11221]
101071639  [KO:K05411]
101071975  [KO:K04456] [EC:2.7.11.1]
101072065  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101072127  tlr1; toll-like receptor 1 [KO:K05398]
101072152  [KO:K00922] [EC:2.7.1.153]
101072751  nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
101073092  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101073138  [KO:K03160]
101073575  [KO:K04440] [EC:2.7.11.24]
101073734  [KO:K04456] [EC:2.7.11.1]
101073743  [KO:K04735]
101073869  [KO:K04433] [EC:2.7.12.2]
101074026  [KO:K04441] [EC:2.7.11.24]
101074146  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
101074428  [KO:K04441] [EC:2.7.11.24]
101074686  [KO:K05404]
101075191  [KO:K04398] [EC:3.4.22.61]
101075631  [KO:K04398] [EC:3.4.22.61]
101076867  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101077059  [KO:K04448]
101077380  pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101077588  [KO:K05425]
101078177  [KO:K04379]
101078355  [KO:K05402]
101078496  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101078548  [KO:K04440] [EC:2.7.11.24]
101078980  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101079608  [KO:K04456] [EC:2.7.11.1]
101079646  [KO:K11220]
101079698  [KO:K02649]
101080001  il1b; interleukin-1 beta [KO:K04519]
101080181  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101080190  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
105417042  [KO:K05412]
105418180  [KO:K10030]
115246422  [KO:K10170]
115246498  [KO:K02373]
115247888  [KO:K05406]
115248712  [KO:K04734]
115251511  [KO:K05414]
115251936  [KO:K05402]
445913  IL-12_p40; interleukin-12 p40 precursor [KO:K05425]
445923  il8; interleukin 8 precursor [KO:K10030]
446069  il12a; interleukin-12 subunit alpha precursor [KO:K05406]
503562  il-6; interleukin-6 precursor [KO:K05405]
654303  tnfa; tumor necrosis factor alpha [KO:K03156]
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
Related
pathway
tru04010  MAPK signaling pathway
tru04060  Cytokine-cytokine receptor interaction
tru04120  Ubiquitin mediated proteolysis
tru04210  Apoptosis
KO pathway
ko04620   

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