KEGG   PATHWAY: zca04620
Entry
zca04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Zalophus californianus (California sea lion)
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
zca04620  Toll-like receptor signaling pathway
zca04620

Organism
Zalophus californianus (California sea lion) [GN:zca]
Gene
113908216  MAP2K6; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
113908217  CCL3L3; C-C motif chemokine 3-like 1 [KO:K05408]
113908218  [KO:K12964]
113908816  TRAF3; LOW QUALITY PROTEIN: TNF receptor-associated factor 3 [KO:K03174]
113908976  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
113908979  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
113910017  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113910226  NFKBIA; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
113910278  FOS; proto-oncogene c-Fos [KO:K04379]
113910424  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
113911273  IRF5; interferon regulatory factor 5 [KO:K09446]
113911688  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113911910  IL6; interleukin-6 [KO:K05405]
113912225  [KO:K05414]
113912320  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113913314  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
113913973  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
113914747  FADD; FAS-associated death domain protein [KO:K02373]
113914759  [KO:K05402]
113914776  [KO:K05403]
113914873  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
113914948  RELA; transcription factor p65 [KO:K04735]
113915477  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
113916105  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
113916214  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
113916429  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
113916493  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
113916510  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
113917006  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
113917022  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113917179  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113917379  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
113917950  [KO:K10161]
113918089  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
113918381  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
113918869  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
113918898  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113919574  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
113919983  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
113919987  [KO:K04392]
113921522  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
113921975  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
113921986  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
113922054  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
113922098  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
113922141  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
113922602  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113923113  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
113923411  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113924180  IKBKB; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113924266  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113924626  TLR1; toll-like receptor 1 [KO:K05398]
113924627  TLR6; toll-like receptor 6 [KO:K10169]
113924725  CXCL9; LOW QUALITY PROTEIN: C-X-C motif chemokine 9 [KO:K05416]
113924761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113924907  CXCL11; C-X-C motif chemokine 11 [KO:K12672]
113924908  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
113925270  CXCL8; interleukin-8 [KO:K10030]
113925290  SPP1; osteopontin isoform X1 [KO:K06250]
113925471  TLR2; toll-like receptor 2 [KO:K10159]
113925863  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
113925885  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
113926549  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
113926671  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
113927116  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
113927499  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
113927705  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
113927740  TNF; tumor necrosis factor [KO:K03156]
113928769  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
113928818  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
113928897  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113929013  CD14; LOW QUALITY PROTEIN: monocyte differentiation antigen CD14 [KO:K04391]
113929340  IL12B; interleukin-12 subunit beta [KO:K05425]
113930597  [KO:K07210]
113930605  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
113931151  [KO:K02373]
113931155  [KO:K09446]
113931272  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
113931499  TLR8; toll-like receptor 8 [KO:K10170]
113931554  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
113932035  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113932378  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
113932728  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
113933258  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
113933356  TLR5; LOW QUALITY PROTEIN: toll-like receptor 5 [KO:K10168]
113934419  IFNB1; interferon beta [KO:K05415]
113934655  [KO:K05414]
113934667  [KO:K05414]
113934678  [KO:K05414]
113934682  [KO:K05414]
113934760  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
113934985  [KO:K05414]
113935537  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113936398  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
113937054  [KO:K05399]
113937839  IL1B; interleukin-1 beta [KO:K04519]
113937934  [KO:K05399]
113938082  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
113939090  [KO:K05408]
113939093  CCL5; C-C motif chemokine 5 [KO:K12499]
113939569  JUN; transcription factor AP-1 [KO:K04448]
113939711  [KO:K05408]
113939775  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
113939897  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
118356554  [KO:K07210]
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
zca04010  MAPK signaling pathway
zca04060  Cytokine-cytokine receptor interaction
zca04064  NF-kappa B signaling pathway
zca04120  Ubiquitin mediated proteolysis
zca04151  PI3K-Akt signaling pathway
zca04210  Apoptosis
zca04610  Complement and coagulation cascades
zca04630  JAK-STAT signaling pathway
KO pathway
ko04620   

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