KEGG   PATHWAY: oro04620
Entry
oro04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Odobenus rosmarus divergens (Pacific walrus)
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
oro04620  Toll-like receptor signaling pathway
oro04620

Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:oro]
Gene
101362806  TLR1; toll-like receptor 1 [KO:K05398]
101363280  TLR2; toll-like receptor 2 [KO:K10159]
101367407  uncharacterized protein LOC101367407 [KO:K10159]
101367518  TLR6; toll-like receptor 6 [KO:K10169]
101372232  LBP; lipopolysaccharide-binding protein isoform X1 [KO:K05399]
101370586  lipopolysaccharide-binding protein-like [KO:K05399]
101376703  CD14; monocyte differentiation antigen CD14 [KO:K04391]
101365004  LY96; lymphocyte antigen 96 [KO:K05400]
101378402  TLR3; toll-like receptor 3 [KO:K05401]
101371071  TLR4; toll-like receptor 4 [KO:K10160]
101363671  TLR5; LOW QUALITY PROTEIN: toll-like receptor 5 [KO:K10168]
101370150  TLR7; toll-like receptor 7 [KO:K05404]
101369550  TLR8; toll-like receptor 8 [KO:K10170]
101371209  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101370160  toll-like receptor 9 isoform X2 [KO:K10161]
101378519  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
101366544  LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
101370689  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101385241  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101385267  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101374787  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101370100  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101371800  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101383166  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101382320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101374757  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101379043  TOLLIP; toll-interacting protein [KO:K05402]
101363951  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101375779  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
101385048  FADD; FAS-associated death domain protein [KO:K02373]
101365855  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101380365  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101382179  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
101362953  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101369401  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101369627  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101376824  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101384959  IKBKG; NF-kappa-B essential modulator isoform X2 [KO:K07210]
101364103  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101375346  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101384149  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101371488  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101381225  RELA; transcription factor p65 [KO:K04735]
101385184  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
101365373  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101376586  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101372573  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101382213  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101378651  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
101382167  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
101386473  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]
101382078  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101377143  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101377430  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101382259  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101382558  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101367488  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101374143  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
101376185  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101368207  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
101366773  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101368209  TNF; tumor necrosis factor [KO:K03156]
101383005  IL1B; interleukin-1 beta [KO:K04519]
101377851  IL6; interleukin-6 isoform X1 [KO:K05405]
101367178  IL12A; interleukin-12 subunit alpha [KO:K05406]
101372789  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
101365039  CXCL8; interleukin-8 [KO:K10030]
101381338  CCL5; LOW QUALITY PROTEIN: C-C motif chemokine 5 [KO:K12499]
101370944  C-C motif chemokine 3 [KO:K05408]
101371244  C-C motif chemokine 3-like [KO:K05408]
101371529  regakine-1-like [KO:K05408]
105758121  C-C motif chemokine 3-like [KO:K05408]
101370656  CCL4; C-C motif chemokine 4 isoform X1 [KO:K12964]
105757540  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
101371542  TICAM1; TIR domain-containing adapter molecule 1 isoform X2 [KO:K05842]
101363053  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101369106  IRF5; interferon regulatory factor 5 [KO:K09446]
101363526  LOW QUALITY PROTEIN: interferon regulatory factor 5-like [KO:K09446]
101374020  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
101386416  SPP1; osteopontin isoform X1 [KO:K06250]
101366827  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
101362394  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
101374855  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101386524  IRF3; interferon regulatory factor 3 [KO:K05411]
101381578  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
101363230  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
101386232  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
101377641  interferon alpha-1/2-like [KO:K05414]
101378214  IFNA5; interferon alpha-5 [KO:K05414]
101374322  interferon alpha-1/2-like [KO:K05414]
101374610  interferon alpha-14-like [KO:K05414]
101379735  interferon beta-like [KO:K05414]
101374900  IFNB1; interferon beta [KO:K05415]
101370046  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101386107  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
101365648  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101377296  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
101378785  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101368050  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101379624  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
101379926  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
101380226  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
101379640  CXCL11; C-X-C motif chemokine 11 [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
oro04010  MAPK signaling pathway
oro04060  Cytokine-cytokine receptor interaction
oro04064  NF-kappa B signaling pathway
oro04120  Ubiquitin mediated proteolysis
oro04151  PI3K-Akt signaling pathway
oro04210  Apoptosis
oro04610  Complement and coagulation cascades
oro04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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