KEGG   PATHWAY: pdic04620
Entry
pdic04620                   Pathway                                
Name
Toll-like receptor signaling pathway - Phyllostomus discolor (pale spear-nosed bat)
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
pdic04620  Toll-like receptor signaling pathway
pdic04620

Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114493408  TLR1; toll-like receptor 1 [KO:K05398]
114503036  TLR2; toll-like receptor 2 [KO:K10159]
114493313  TLR6; toll-like receptor 6 [KO:K10169]
114506680  lipopolysaccharide-binding protein isoform X1 [KO:K05399]
114506119  lipopolysaccharide-binding protein-like [KO:K05399]
114510320  CD14; monocyte differentiation antigen CD14 [KO:K04391]
114501897  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
114508609  TLR3; toll-like receptor 3 [KO:K05401]
114510836  TLR4; toll-like receptor 4 isoform X2 [KO:K10160]
114512329  TLR5; toll-like receptor 5 isoform X1 [KO:K10168]
114505233  TLR7; toll-like receptor 7 [KO:K05404]
114505753  TLR8; toll-like receptor 8 [KO:K10170]
114489030  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
114502022  TLR9; LOW QUALITY PROTEIN: toll-like receptor 9 [KO:K10161]
114509515  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
114497407  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114490993  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114501452  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114496100  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114502559  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
114501063  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114510957  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114512350  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114492688  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114501591  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
114509653  toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
114489990  FADD; FAS-associated death domain protein [KO:K02373]
114494575  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
114514079  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
114505021  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X3 [KO:K04730] [EC:2.7.11.1]
114500758  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
114513395  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
114495234  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X2 [KO:K04404]
114493958  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
114504586  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
114496345  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
114508493  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
114492937  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
114492465  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
114499888  RELA; transcription factor p65 [KO:K04735]
114491904  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X2 [KO:K04415] [EC:2.7.11.25]
114491735  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
114503388  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114510156  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114496946  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114515272  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
114503069  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
114514974  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
114515070  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
114513098  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114513304  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
114493876  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114493878  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
114509631  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
114496029  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
114492422  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114496428  JUN; transcription factor AP-1 [KO:K04448]
114493153  FOS; proto-oncogene c-Fos [KO:K04379]
114495334  TNF; tumor necrosis factor isoform X1 [KO:K03156]
114500536  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
114508090  IL6; interleukin-6 isoform X1 [KO:K05405]
114491057  IL12A; interleukin-12 subunit alpha [KO:K05406]
114510060  IL12B; interleukin-12 subunit beta [KO:K05425]
118499766  C-X-C motif chemokine 15-like isoform X1 [KO:K10030]
114493304  CXCL8; interleukin-8 [KO:K10030]
114504281  CCL5; C-C motif chemokine 5 [KO:K12499]
114502361  C-C motif chemokine 3-like [KO:K05408]
114503560  C-C motif chemokine 3-like 1 isoform X1 [KO:K05408]
114503979  C-C motif chemokine 3-like [KO:K05408]
114504229  C-C motif chemokine 3-like [KO:K05408]
114503455  C-C motif chemokine 4 [KO:K12964]
114503501  C-C motif chemokine 4-like [KO:K12964]
114502817  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
114497608  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
114507644  IRF5; interferon regulatory factor 5 isoform X4 [KO:K09446]
114499187  IRF7; interferon regulatory factor 7 [KO:K09447]
114492326  SPP1; osteopontin [KO:K06250]
114512155  IKBKE; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
114513223  TBK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
114492329  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
114511489  IRF3; interferon regulatory factor 3 [KO:K05411]
114506775  CD40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
114488801  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
114490803  CD86; T-lymphocyte activation antigen CD86 isoform X6 [KO:K05413]
114502765  interferon alpha-4-like [KO:K05414]
114502773  interferon alpha-4-like [KO:K05414]
114503306  interferon alpha-4-like [KO:K05414]
114490854  interferon alpha-4-like [KO:K05414]
114490401  interferon alpha-4-like [KO:K05414]
114512515  IFNB1; interferon beta [KO:K05415]
114490062  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
114490003  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
114498103  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
114502963  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
114494120  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
114513273  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
114492081  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
118499832  CXCL10; C-X-C motif chemokine 10 isoform X1 [KO:K12671]
114496089  LOW QUALITY PROTEIN: C-X-C motif chemokine 10 [KO:K12671]
114493309  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
114491884  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
pdic04010  MAPK signaling pathway
pdic04060  Cytokine-cytokine receptor interaction
pdic04064  NF-kappa B signaling pathway
pdic04120  Ubiquitin mediated proteolysis
pdic04151  PI3K-Akt signaling pathway
pdic04210  Apoptosis
pdic04610  Complement and coagulation cascades
pdic04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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