KEGG   PATHWAY: mmf04620
Entry
mmf04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Molossus molossus (Pallas's mastiff 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
mmf04620  Toll-like receptor signaling pathway
mmf04620

Organism
Molossus molossus (Pallas's mastiff bat) [GN:mmf]
Gene
118616119  TLR2; toll-like receptor 2 [KO:K10159]
118626267  TLR6; toll-like receptor 6 [KO:K10169]
118618447  LOW QUALITY PROTEIN: lipopolysaccharide-binding protein [KO:K05399]
118618911  lipopolysaccharide-binding protein-like [KO:K05399]
118615605  CD14; monocyte differentiation antigen CD14 [KO:K04391]
118631426  LY96; lymphocyte antigen 96 [KO:K05400]
118622536  TLR3; toll-like receptor 3 [KO:K05401]
118629497  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
118640576  TLR5; toll-like receptor 5 [KO:K10168]
118636314  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
118636426  TLR8; toll-like receptor 8 [KO:K10170]
118637271  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
118633316  toll-like receptor 9 isoform X1 [KO:K10161]
118616519  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
118632927  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626944  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118617106  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118626685  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118642883  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118616460  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118640620  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118619617  LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
118630299  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118638405  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118643200  toll-interacting protein [KO:K05402]
118633334  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
118640256  toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
118628258  FADD; FAS-associated death domain protein [KO:K02373]
118625346  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
118624132  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
118636423  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
118628151  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
118623445  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
118620813  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
118621083  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
118635619  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118632312  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
118622317  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
118617230  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
118624789  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118628367  RELA; transcription factor p65 [KO:K04735]
118639002  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
118628434  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
118615385  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
118640210  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118642307  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
118641294  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
118634140  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
118633861  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
118615560  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
118641186  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118641187  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
118621004  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118621005  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118642157  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118615122  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118632456  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118627223  JUN; transcription factor AP-1 [KO:K04448]
118618599  FOS; proto-oncogene c-Fos [KO:K04379]
118621647  TNF; tumor necrosis factor [KO:K03156]
118630740  IL1B; interleukin-1 beta [KO:K04519]
118620458  IL6; interleukin-6 isoform X1 [KO:K05405]
118617678  IL12A; interleukin-12 subunit alpha [KO:K05406]
118615760  IL12B; interleukin-12 subunit beta [KO:K05425]
118626319  C-X-C motif chemokine 15-like [KO:K10030]
118636257  interleukin-8-like [KO:K10030]
118643469  CXCL8; interleukin-8 [KO:K10030]
118634388  CCL5; C-C motif chemokine 5 [KO:K12499]
118634314  C-C motif chemokine 3-like [KO:K05408]
118634427  C-C motif chemokine 3 [KO:K05408]
118634379  C-C motif chemokine 4 [KO:K12964]
118634535  C-C motif chemokine 4-like [KO:K12964]
118642387  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
118615402  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
118626388  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
118616944  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
118620151  IRF5; interferon regulatory factor 5 [KO:K09446]
118643167  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
118639020  SPP1; osteopontin [KO:K06250]
118637482  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
118624185  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
118633499  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
118639395  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
118618725  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
118617671  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
118617834  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
118629333  interferon omega-1-like [KO:K05414]
118629850  interferon alpha-14-like [KO:K05414]
118629329  IFNB1; interferon beta [KO:K05415]
118617107  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
118617288  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
118626049  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
118615353  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
118625659  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
118623876  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
118631124  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
118618117  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
118620671  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
118618109  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
mmf04010  MAPK signaling pathway
mmf04060  Cytokine-cytokine receptor interaction
mmf04064  NF-kappa B signaling pathway
mmf04120  Ubiquitin mediated proteolysis
mmf04151  PI3K-Akt signaling pathway
mmf04210  Apoptosis
mmf04610  Complement and coagulation cascades
mmf04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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