KEGG   PATHWAY: rno04620
Entry
rno04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Rattus norvegicus (rat)
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
rno04620  Toll-like receptor signaling pathway
rno04620

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
305354  Tlr1; toll-like receptor 1 precursor [KO:K05398]
310553  Tlr2; toll-like receptor 2 precursor [KO:K10159]
305353  Tlr6; toll-like receptor 6 [KO:K10169]
29469  Lbp; lipopolysaccharide-binding protein precursor [KO:K05399]
60350  Cd14; monocyte differentiation antigen CD14 precursor [KO:K04391]
448830  Ly96; lymphocyte antigen 96 precursor [KO:K05400]
364594  Tlr3; toll-like receptor 3 precursor [KO:K05401]
29260  Tlr4; toll-like receptor 4 precursor [KO:K10160]
289337  Tlr5; toll-like receptor 5 [KO:K10168]
317468  Tlr7; toll-like receptor 7 [KO:K05404]
684440  Tlr8; toll-like receptor 8 precursor [KO:K10170]
29175  Ctsk; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
338457  Tlr9; toll-like receptor 9 precursor [KO:K10161]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
361677  Tollip; toll-interacting protein [KO:K05402]
301059  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
680127  Tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
300177  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
363520  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
315139  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
308267  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
116596  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
303200  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
114495  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
287398  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431] [EC:2.7.12.2]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516  Jun; transcription factor Jun [KO:K04448]
314322  Fos; protein c-Fos [KO:K04379]
24835  Tnf; tumor necrosis factor [KO:K03156]
24494  Il1b; interleukin-1 beta [KO:K04519]
24498  Il6; interleukin-6 precursor [KO:K05405]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
81780  Ccl5; C-C motif chemokine 5 precursor [KO:K12499]
25542  Ccl3; C-C motif chemokine 3 precursor [KO:K05408]
116637  Ccl4; C-C motif chemokine 4 precursor [KO:K12964]
364867  Ticam2; TIR domain-containing adapter molecule 2 [KO:K05409]
363328  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
306886  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
296953  Irf5; interferon regulatory factor 5 [KO:K09446]
293624  Irf7; interferon regulatory factor 7 [KO:K09447]
25353  Spp1; osteopontin precursor [KO:K06250]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
299827  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
362788  Traf3; TNF receptor-associated factor 3 [KO:K03174]
292892  Irf3; interferon regulatory factor 3 [KO:K05411]
171369  Cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
25408  Cd80; T-lymphocyte activation antigen CD80 [KO:K05412]
56822  Cd86; T-lymphocyte activation antigen CD86 precursor [KO:K05413]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha family, gene 5 precursor [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  Ifna4l2; similar to Interferon alpha-1 precursor [KO:K05414]
500491  Ifna16l1; interferon, alpha 16-like 1 precursor [KO:K05414]
134487075  interferon alpha-1-like [KO:K05414]
134487077  interferon alpha-1-like [KO:K05414]
100911527  Ifna4l1; interferon alpha-11-like [KO:K05414]
100912356  interferon alpha-1-like precursor [KO:K05414]
502959  Ifna1l1; similar to put. precursor MuIFN-alpha 5 precursor [KO:K05414]
24481  Ifnb1; interferon beta precursor [KO:K05415]
288264  Ifnar1; interferon alpha/beta receptor 1 isoform 1 precursor [KO:K05130]
686326  Ifnar2; interferon alpha and beta receptor subunit 2 isoform 1 precursor [KO:K05131]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
246759  Cxcl9; C-X-C motif chemokine 9 precursor [KO:K05416]
305236  Cxcl11; C-X-C motif chemokine 11 precursor [KO:K12672]
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
rno04010  MAPK signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04064  NF-kappa B signaling pathway
rno04120  Ubiquitin mediated proteolysis
rno04151  PI3K-Akt signaling pathway
rno04210  Apoptosis
rno04610  Complement and coagulation cascades
rno04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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