KEGG   PATHWAY: mlx04620
Entry
mlx04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Mirounga leonina (Southern elephant seal)
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
mlx04620  Toll-like receptor signaling pathway
mlx04620

Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997742  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
117997743  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
117998287  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
117998440  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
117998660  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
117998991  [KO:K05414]
117998992  [KO:K05414]
117998993  [KO:K05414]
117998994  IFNB1; interferon beta [KO:K05415]
117999009  [KO:K05414]
117999338  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
117999637  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999826  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118000083  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
118000167  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
118000314  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
118001048  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
118001095  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118001265  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118001330  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
118001922  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
118002024  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118002212  FOS; proto-oncogene c-Fos [KO:K04379]
118002595  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
118002835  [KO:K04734]
118002880  [KO:K04734]
118003336  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118003729  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
118004424  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
118004882  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
118004942  [KO:K10161]
118004956  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
118005180  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
118005289  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
118005789  IL12A; interleukin-12 subunit alpha [KO:K05406]
118006042  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118006556  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
118007039  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
118007066  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
118007867  IL1B; interleukin-1 beta [KO:K04519]
118008624  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
118008707  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
118008943  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
118009921  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
118010049  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
118010349  SPP1; osteopontin isoform X1 [KO:K06250]
118010368  [KO:K04440] [EC:2.7.11.24]
118010433  CXCL9; C-X-C motif chemokine 9 isoform X1 [KO:K05416]
118010434  CXCL11; C-X-C motif chemokine 11 [KO:K12672]
118010435  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
118010458  CXCL8; interleukin-8 [KO:K10030]
118010615  TLR6; toll-like receptor 6 [KO:K10169]
118010898  TLR1; toll-like receptor 1 [KO:K05398]
118011138  LBP; lipopolysaccharide-binding protein [KO:K05399]
118011474  [KO:K05399]
118011553  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
118012152  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
118012204  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
118012989  TLR5; LOW QUALITY PROTEIN: toll-like receptor 5 [KO:K10168]
118013385  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
118014127  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
118014480  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118014553  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118014698  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
118014931  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
118015773  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
118016059  RELA; transcription factor p65 [KO:K04735]
118016150  IL12B; interleukin-12 subunit beta [KO:K05425]
118016168  FADD; FAS-associated death domain protein [KO:K02373]
118016203  TOLLIP; toll-interacting protein [KO:K05402]
118016222  IRF7; interferon regulatory factor 7 [KO:K09447]
118016541  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
118016718  CD14; monocyte differentiation antigen CD14 [KO:K04391]
118016863  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118017761  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
118018155  [KO:K04392]
118018829  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
118018831  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
118019316  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
118019356  JUN; transcription factor AP-1 [KO:K04448]
118019468  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118020028  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118020856  IL6; interleukin-6 [KO:K05405]
118021067  IRF5; interferon regulatory factor 5 isoform X1 [KO:K09446]
118022230  TLR2; toll-like receptor 2 [KO:K10159]
118022538  [KO:K10159]
118022658  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118022776  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118024329  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
118024640  [KO:K05408]
118024642  [KO:K05408]
118024839  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
118025020  CCL5; C-C motif chemokine 5 [KO:K12499]
118025022  [KO:K12964]
118026506  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118026716  TLR7; toll-like receptor 7 [KO:K05404]
118026718  TLR8; toll-like receptor 8 isoform X1 [KO:K10170]
118027047  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118027255  TNF; tumor necrosis factor [KO:K03156]
118027395  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
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
mlx04010  MAPK signaling pathway
mlx04060  Cytokine-cytokine receptor interaction
mlx04064  NF-kappa B signaling pathway
mlx04120  Ubiquitin mediated proteolysis
mlx04151  PI3K-Akt signaling pathway
mlx04210  Apoptosis
mlx04610  Complement and coagulation cascades
mlx04630  JAK-STAT signaling pathway
KO pathway
ko04620   

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