KEGG   PATHWAY: hhv04620
Entry
hhv04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Hyaena hyaena (striped hyena)
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
hhv04620  Toll-like receptor signaling pathway
hhv04620

Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120228518  TLR1; toll-like receptor 1 [KO:K05398]
120233209  TLR2; toll-like receptor 2 isoform X1 [KO:K10159]
120228517  TLR6; toll-like receptor 6 [KO:K10169]
120228582  lipopolysaccharide-binding protein-like [KO:K05399]
120228614  LOW QUALITY PROTEIN: lipopolysaccharide-binding protein [KO:K05399]
120245610  CD14; monocyte differentiation antigen CD14 [KO:K04391]
120235879  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
120237778  TLR3; toll-like receptor 3 [KO:K05401]
120240966  TLR4; toll-like receptor 4 [KO:K10160]
120234151  TLR5; toll-like receptor 5 [KO:K10168]
120233135  TLR7; toll-like receptor 7 [KO:K05404]
120233136  TLR8; toll-like receptor 8 [KO:K10170]
120241249  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
120239421  toll-like receptor 9 isoform X1 [KO:K10161]
120227958  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
120233608  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120220979  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120246696  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120219997  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120239233  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120247089  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
120235277  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120244696  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120247774  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120225940  toll-interacting protein isoform X1 [KO:K05402]
120235110  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
120247108  toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
120233869  FADD; FAS-associated death domain protein [KO:K02373]
120220675  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
120246010  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
120221716  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
120232555  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
120233644  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
120237570  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
120231881  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
120226622  IKBKG; NF-kappa-B essential modulator [KO:K07210]
120243217  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
120233999  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
120248609  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
120222817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
120240185  RELA; transcription factor p65 [KO:K04735]
120221616  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
120221655  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120242086  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
120238830  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120242212  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
120228759  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
120230246  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
120231429  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
120244848  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
120233796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120233829  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120234701  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120235253  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
120244180  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120232781  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120245677  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
120236252  JUN; transcription factor AP-1 [KO:K04448]
120231952  FOS; proto-oncogene c-Fos [KO:K04379]
120221913  TNF; tumor necrosis factor [KO:K03156]
120231517  IL1B; interleukin-1 beta [KO:K04519]
120236228  IL6; interleukin-6 isoform X1 [KO:K05405]
120238298  IL12A; interleukin-12 subunit alpha [KO:K05406]
120240593  IL12B; interleukin-12 subunit beta [KO:K05425]
120231052  CXCL8; interleukin-8 [KO:K10030]
120224392  CCL5; C-C motif chemokine 5 [KO:K12499]
120227747  C-C motif chemokine 3-like [KO:K05408]
120227778  C-C motif chemokine 4-like [KO:K12964]
120245510  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
120242077  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
120241444  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
120238853  IRF5; interferon regulatory factor 5 [KO:K09446]
120223400  IRF7; interferon regulatory factor 7 [KO:K09447]
120226352  SPP1; osteopontin isoform X1 [KO:K06250]
120228866  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
120233179  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
120244583  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
120244065  IRF3; interferon regulatory factor 3 [KO:K05411]
120243315  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
120225963  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
120237392  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
120239878  interferon alpha-like [KO:K05414]
120223241  interferon alpha-like [KO:K05414]
120223242  interferon alpha-like [KO:K05414]
120239877  IFNB1; interferon beta [KO:K05415]
120229314  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
120229615  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
120232606  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
120244482  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
120233455  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
120219936  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
120247003  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
120231068  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
120231066  CXCL9; C-X-C motif chemokine 9 isoform X1 [KO:K05416]
120231069  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
hhv04010  MAPK signaling pathway
hhv04060  Cytokine-cytokine receptor interaction
hhv04064  NF-kappa B signaling pathway
hhv04120  Ubiquitin mediated proteolysis
hhv04151  PI3K-Akt signaling pathway
hhv04210  Apoptosis
hhv04610  Complement and coagulation cascades
hhv04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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