KEGG   PATHWAY: hmh04620
Entry
hmh04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Hylobates moloch (silvery gibbon)
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
hmh04620  Toll-like receptor signaling pathway
hmh04620

Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116456218  FOS; protein c-Fos [KO:K04379]
116456827  TLR6; toll-like receptor 6 [KO:K10169]
116456828  TLR1; toll-like receptor 1 [KO:K05398]
116457363  JUN; transcription factor Jun [KO:K04448]
116457541  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
116457771  TLR5; toll-like receptor 5 [KO:K10168]
116457829  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
116457855  [KO:K05842]
116457903  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116458330  [KO:K05414]
116458331  [KO:K05414]
116458332  [KO:K05414]
116458518  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
116458519  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116458527  [KO:K05414]
116458611  [KO:K05414]
116458660  [KO:K05414]
116458812  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
116458843  IFNB1; interferon beta [KO:K05415]
116459126  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116459332  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]
116459642  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116459649  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116459720  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
116460115  TNF; tumor necrosis factor isoform X2 [KO:K03156]
116460769  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116461078  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
116461447  SPP1; osteopontin isoform X1 [KO:K06250]
116461488  LBP; lipopolysaccharide-binding protein [KO:K05399]
116461632  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
116462065  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
116462105  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116462749  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116463128  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116463159  [KO:K04404]
116463202  [KO:K04404]
116463392  [KO:K05406]
116463424  [KO:K05406]
116464818  IKBKG; NF-kappa-B essential modulator isoform X2 [KO:K07210]
116465400  TLR2; toll-like receptor 2 [KO:K10159]
116466084  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
116466580  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
116466780  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
116466788  CXCL11; C-X-C motif chemokine 11 isoform X1 [KO:K12672]
116466806  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
116466874  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
116466907  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
116467002  CXCL8; interleukin-8 [KO:K10030]
116469011  RELA; transcription factor p65 isoform X1 [KO:K04735]
116469121  FADD; FAS-associated death domain protein [KO:K02373]
116469167  TOLLIP; toll-interacting protein isoform X1 [KO:K05402]
116469475  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
116469793  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
116470222  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116470920  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
116471599  CD14; monocyte differentiation antigen CD14 [KO:K04391]
116471783  IL12B; interleukin-12 subunit beta [KO:K05425]
116471970  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116473104  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
116473405  [KO:K10161]
116473667  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
116474111  [KO:K05408]
116474525  CCL3L3; C-C motif chemokine 3-like 1 [KO:K05408]
116474526  [KO:K12964]
116474527  CCL5; C-C motif chemokine 5 [KO:K12499]
116475593  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
116476347  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
116477149  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
116478197  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
116478375  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116478444  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
116478691  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116480287  [KO:K04392]
116480683  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116480802  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
116480910  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
116481090  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
116481263  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116481707  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
116482295  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116482629  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
116483006  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
116483283  IL1B; interleukin-1 beta [KO:K04519]
116483343  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116483533  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
116483548  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116483711  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
116484638  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
116484959  IRF9; interferon regulatory factor 9 [KO:K04693]
116485121  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116485139  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116485188  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
116810454  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
116810529  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
116810870  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116810998  TLR8; toll-like receptor 8 [KO:K10170]
116811520  TLR7; toll-like receptor 7 [KO:K05404]
116812171  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
116812651  LY96; lymphocyte antigen 96 [KO:K05400]
116812889  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116813186  IL6; interleukin-6 isoform X1 [KO:K05405]
116814338  IRF5; interferon regulatory factor 5 isoform X1 [KO:K09446]
116814342  [KO:K04369] [EC:2.7.12.2]
Reference
PMID:17275323
  Authors
Kawai T, Akira S.
  Title
TLR signaling.
  Journal
Semin Immunol 19:24-32 (2007)
DOI:10.1016/j.smim.2006.12.004
Reference
PMID:17457343
  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
PMID:16932750
  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
PMID:17395581
  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
PMID:16497588
  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
PMID:14698224
  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
PMID:12734364
  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
PMID:14751764
  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
PMID:17637696
  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
PMID:17507094
  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
PMID:11101877
  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
PMID:16924467
  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
hmh04010  MAPK signaling pathway
hmh04060  Cytokine-cytokine receptor interaction
hmh04064  NF-kappa B signaling pathway
hmh04120  Ubiquitin mediated proteolysis
hmh04151  PI3K-Akt signaling pathway
hmh04210  Apoptosis
hmh04610  Complement and coagulation cascades
hmh04630  JAK-STAT signaling pathway
KO pathway
ko04620   

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