KEGG   PATHWAY: mjv04620
Entry
mjv04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Manis javanica (Malayan pangolin)
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
mjv04620  Toll-like receptor signaling pathway
mjv04620

Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108383754  [KO:K05408]
108383755  [KO:K12964]
108383756  [KO:K05408]
108384893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108385046  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X3 [KO:K04369] [EC:2.7.12.2]
108385635  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
108386817  JUN; transcription factor Jun [KO:K04448]
108390202  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
108390300  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108390634  TLR2; toll-like receptor 2 [KO:K10159]
108391263  IRF9; interferon regulatory factor 9 [KO:K04693]
108391396  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
108391706  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
108392124  CD14; monocyte differentiation antigen CD14 [KO:K04391]
108392181  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
108392246  CD80; T-lymphocyte activation antigen CD80 isoform X3 [KO:K05412]
108392489  LBP; lipopolysaccharide-binding protein [KO:K05399]
108392844  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
108392900  CD40; tumor necrosis factor receptor superfamily member 5 isoform X3 [KO:K03160]
108393034  IL1B; interleukin-1 beta [KO:K04519]
108393592  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
108394635  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
108394636  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108395975  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
108396408  TLR3; toll-like receptor 3 [KO:K05401]
108396677  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X3 [KO:K04733] [EC:2.7.11.1]
108396943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108397005  RELA; transcription factor p65 isoform X1 [KO:K04735]
108397113  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
108397207  TLR8; toll-like receptor 8 [KO:K10170]
108397208  TLR7; toll-like receptor 7 [KO:K05404]
108397364  [KO:K04403]
108397409  [KO:K05414]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108397877  TNF; tumor necrosis factor [KO:K03156]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108398622  IL6; interleukin-6 [KO:K05405]
108398727  [KO:K10030]
108399058  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
108399127  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
108399262  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
108399795  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108400080  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
108400317  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
108400663  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
108400680  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
108400819  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
108400862  LY96; lymphocyte antigen 96 [KO:K05400]
108401029  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
108401269  SPP1; osteopontin isoform X2 [KO:K06250]
108401442  FADD; FAS-associated death domain protein [KO:K02373]
108401471  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
108401472  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
108402236  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
108402523  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108402531  IFNB1; interferon beta [KO:K05415]
108402534  FOS; protein c-Fos [KO:K04379]
108403349  IRF5; interferon regulatory factor 5 isoform X1 [KO:K09446]
108404439  [KO:K10161]
108405137  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
108405993  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
108406431  TOLLIP; toll-interacting protein [KO:K05402]
108406440  CXCL8; interleukin-8 isoform X1 [KO:K10030]
108406584  TRAF3; TNF receptor-associated factor 3 isoform X3 [KO:K03174]
108407381  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
108407505  CCL5; C-C motif chemokine 5 [KO:K12499]
108407595  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
108407943  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
108408263  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
108408637  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
108409113  IL12A; interleukin-12 subunit alpha [KO:K05406]
108409190  IL12B; interleukin-12 subunit beta [KO:K05425]
108409505  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
108409511  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
108409586  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108409616  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108410067  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
mjv04010  MAPK signaling pathway
mjv04060  Cytokine-cytokine receptor interaction
mjv04064  NF-kappa B signaling pathway
mjv04120  Ubiquitin mediated proteolysis
mjv04151  PI3K-Akt signaling pathway
mjv04210  Apoptosis
mjv04610  Complement and coagulation cascades
mjv04630  JAK-STAT signaling pathway
KO pathway
ko04620   

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