KEGG   PATHWAY: umr04620
Entry
umr04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Ursus maritimus (polar bear)
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
umr04620  Toll-like receptor signaling pathway
umr04620

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103658031  toll-like receptor 2 [KO:K10159]
103672667  TLR6; toll-like receptor 6 [KO:K10169]
103669764  lipopolysaccharide-binding protein-like isoform X1 [KO:K05399]
103669766  lipopolysaccharide-binding protein [KO:K05399]
103663749  CD14; monocyte differentiation antigen CD14 isoform X1 [KO:K04391]
103681265  LY96; lymphocyte antigen 96 [KO:K05400]
103680971  TLR3; toll-like receptor 3 [KO:K05401]
103670382  TLR4; toll-like receptor 4 [KO:K10160]
103667333  TLR5; toll-like receptor 5 isoform X1 [KO:K10168]
103668101  TLR7; toll-like receptor 7 isoform X3 [KO:K05404]
103668102  TLR8; toll-like receptor 8 [KO:K10170]
103667534  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
103670095  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103671110  toll-interacting protein [KO:K05402]
103680724  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
103660655  toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
103671072  FADD; FAS-associated death domain protein [KO:K02373]
103659742  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
103675405  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
103679690  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
103659308  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103676518  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
103666926  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
103660092  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103658916  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103679584  RELA; transcription factor p65 [KO:K04735]
103656496  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103658475  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103665687  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103660510  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
103681888  MAP2K7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103676947  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103679990  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103667893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103670861  JUN; transcription factor AP-1 [KO:K04448]
103671011  FOS; proto-oncogene c-Fos [KO:K04379]
103682322  TNF; tumor necrosis factor [KO:K03156]
103671495  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
103658871  IL6; interleukin-6 [KO:K05405]
103681335  IL12A; interleukin-12 subunit alpha [KO:K05406]
103664531  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
103665307  CXCL8; interleukin-8 [KO:K10030]
103667294  CCL5; C-C motif chemokine 5 [KO:K12499]
103667298  C-C motif chemokine 3-like [KO:K05408]
103667297  C-C motif chemokine 3 [KO:K05408]
103667299  regakine-1-like [KO:K05408]
103667295  C-C motif chemokine 4 isoform X2 [KO:K12964]
103679954  TIR domain-containing adapter molecule 2-like [KO:K05409]
103681847  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
103664964  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
103676645  IRF5; interferon regulatory factor 5 isoform X2 [KO:K09446]
103671092  IRF7; LOW QUALITY PROTEIN: interferon regulatory factor 7 [KO:K09447]
103677885  SPP1; osteopontin isoform X1 [KO:K06250]
103671004  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
103656833  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
103656774  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
103657131  IRF3; interferon regulatory factor 3 [KO:K05411]
103669702  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
103678791  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
103678768  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
103662147  interferon alpha-1/2-like [KO:K05414]
103662148  interferon alpha-1/2-like [KO:K05414]
103662149  interferon alpha-2-like [KO:K05414]
103680385  interferon alpha-1/2-like [KO:K05414]
103680386  interferon alpha-1/2-like [KO:K05414]
103666985  interferon alpha-1/2-like [KO:K05414]
121103043  interferon alpha-1/2-like [KO:K05414]
103662150  IFNB1; interferon beta [KO:K05415]
103673220  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
103673110  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
103663059  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103678725  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
103659933  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
103656206  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
103679279  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
103665330  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
103665327  CXCL9; C-X-C motif chemokine 9 isoform X1 [KO:K05416]
103665329  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
umr04010  MAPK signaling pathway
umr04060  Cytokine-cytokine receptor interaction
umr04064  NF-kappa B signaling pathway
umr04120  Ubiquitin mediated proteolysis
umr04151  PI3K-Akt signaling pathway
umr04210  Apoptosis
umr04610  Complement and coagulation cascades
umr04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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