KEGG   PATHWAY: xtr04620
Entry
xtr04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Xenopus tropicalis (tropical clawed frog)
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
xtr04620  Toll-like receptor signaling pathway
xtr04620

Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
100037849  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
100038172  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100101764  map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100101766  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100134991  tnf; tumor necrosis factor [KO:K03156]
100135013  map2k4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100144709  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100144715  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100144924  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100145045  [KO:K04441] [EC:2.7.11.24]
100145270  ikbkg; NF-kappa-B essential modulator [KO:K07210]
100151703  tlr7; toll-like receptor 7 [KO:K05404]
100170174  stat2; signal transducer and activator of transcription 2 [KO:K11221]
100170194  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100216212  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
100270675  cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
100379789  fadd; FAS-associated death domain protein [KO:K02373]
100485201  [KO:K10159]
100485512  [KO:K10159]
100485771  tlr2; toll-like receptor 2 type-2 [KO:K10159]
100485927  [KO:K10159]
100486083  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100486223  tlr3; toll-like receptor 3 [KO:K05401]
100486350  cd86; T-lymphocyte activation antigen CD86 [KO:K05413]
100486835  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100487038  il1b; interleukin-1 beta [KO:K04519]
100487158  irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]
100487744  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100487973  [KO:K10159]
100489423  [KO:K10168]
100489432  tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
100490038  akt1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100490108  cxcl9; C-X-C motif chemokine 11-1 [KO:K12671]
100490139  [KO:K01371] [EC:3.4.22.38]
100490277  cxcl10; C-X-C motif chemokine 10 [KO:K12671]
100490785  cxcl11; C-X-C motif chemokine 11-1 [KO:K12671]
100491693  [KO:K05403]
100492634  [KO:K01371] [EC:3.4.22.38]
100493069  map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
100493911  jun; transcription factor AP-1 [KO:K04448]
100493914  [KO:K05425]
100493927  il6; interleukin-6 [KO:K05405]
100493946  tlr6; toll-like receptor 1 [KO:K10169]
100494387  tlr9; toll-like receptor 7 [KO:K05404]
100495171  tlr1; toll-like receptor 1 [KO:K05398]
100495326  [KO:K05398]
100495471  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100495962  [KO:K10170]
100496108  tlr8; toll-like receptor 8 [KO:K10170]
100496395  irf7; interferon regulatory factor 7 [KO:K09447]
100496523  ccl5; C-C motif chemokine 5 isoform X3 [KO:K12499]
100496647  [KO:K10168]
100496877  ifnar2.2; interferon alpha/beta receptor 2 [KO:K05131]
100497001  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100497163  ccl4; C-C motif chemokine 4 homolog [KO:K12964]
100498017  cxcl2; interleukin-8 [KO:K10030]
100498216  traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100498234  [KO:K10030]
100498389  [KO:K10030]
100498551  cxcl8; interleukin-8 [KO:K10030]
100498552  ifnar1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
101730379  [KO:K10030]
101730633  [KO:K05408]
101733659  [KO:K05842]
101733943  cd80; T-lymphocyte activation antigen CD80 [KO:K05412]
101734275  irf3; interferon regulatory factor 3 [KO:K05411]
101734580  [KO:K05406]
105945198  [KO:K05414]
105946710  [KO:K12964]
116407924  [KO:K05414]
116408033  [KO:K05414]
116409470  [KO:K10159]
116409688  il12b; interleukin-12 subunit beta isoform X1 [KO:K05425]
116409784  [KO:K04519]
407869  rela; transcription factor p65 [KO:K04735]
448118  rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
448125  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
448132  map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
448138  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
448216  ctsk; cathepsin K (pycnodysostosis) precursor [KO:K01371] [EC:3.4.22.38]
448296  mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
448357  irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
448770  tollip; toll-interacting protein [KO:K05402]
493420  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
493524  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
548954  fos; proto-oncogene c-Fos [KO:K04379]
549217  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
549591  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
549654  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
549834  mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
549881  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
549983  pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
613115  map2k7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
733541  tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
733738  irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
734065  irf5; interferon regulatory factor 5 [KO:K09446]
779515  mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
779845  ifnar2.1; interferon (alpha, beta and omega) receptor 2, gene 1 precursor [KO:K05131]
779889  ctsk; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
779958  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
780390  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
780397  stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
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
xtr04010  MAPK signaling pathway
xtr04060  Cytokine-cytokine receptor interaction
xtr04120  Ubiquitin mediated proteolysis
xtr04210  Apoptosis
KO pathway
ko04620   

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