KEGG   PATHWAY: bbub04620
Entry
bbub04620                   Pathway                                
Name
Toll-like receptor signaling pathway - Bubalus bubalis (water buffalo)
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
bbub04620  Toll-like receptor signaling pathway
bbub04620

Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102390405  TLR5; toll-like receptor 5 [KO:K10168]
102391021  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
102391709  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102392112  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102392310  CCL5; C-C motif chemokine 5 isoform X1 [KO:K12499]
102392559  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
102392837  LY96; lymphocyte antigen 96 precursor [KO:K05400]
102393434  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
102393701  [KO:K05414]
102393791  FOS; proto-oncogene C-Fos [KO:K04379]
102393818  [KO:K05414]
102394317  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102394367  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
102394430  [KO:K05399]
102394706  IKBKG; NF-kappa-B essential modulator isoform X6 [KO:K07210]
102394946  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102395178  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X4 [KO:K04430] [EC:2.7.12.2]
102395384  [KO:K02649]
102395411  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102395598  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
102395805  CD40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
102396206  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102396262  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
102396505  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
102396572  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
102396674  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
102396744  IRF5; interferon regulatory factor 5 isoform X1 [KO:K09446]
102396842  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102397128  TLR6; toll-like receptor 6 [KO:K10169]
102397149  MAPK14; mitogen-activated protein kinase 14 isoform X4 [KO:K04441] [EC:2.7.11.24]
102397694  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102397791  TLR2; toll-like receptor 2 isoform X1 [KO:K10159]
102397938  RELA; transcription factor P65 [KO:K04735]
102397969  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102397985  FADD; FAS-associated death domain protein [KO:K02373]
102398659  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X4 [KO:K07211] [EC:2.7.11.10]
102398761  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102398886  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102399138  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102399257  CD14; monocyte differentiation antigen CD14 isoform X1 [KO:K04391]
102399287  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102399580  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102399613  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
102400519  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102401744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102402056  [KO:K05415]
102402213  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102402262  TRAF3; TNF receptor-associated factor 3 isoform X2 [KO:K03174]
102402367  [KO:K05415]
102402697  [KO:K05415]
102402789  [KO:K05414]
102402850  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102402933  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102403043  SPP1; osteopontin [KO:K06250]
102403288  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
102403296  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102403452  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
102403644  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102403930  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
102404165  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102404517  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102404610  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102404626  [KO:K05403]
102404837  CD80; T-lymphocyte activation antigen CD80 isoform X3 [KO:K05412]
102404881  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
102405224  JUN; transcription factor AP-1 [KO:K04448]
102405285  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102406557  CD86; T-lymphocyte activation antigen CD86 isoform X2 [KO:K05413]
102406980  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
102407022  TLR4; toll-like receptor 4 precursor [KO:K10160]
102407535  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102408434  [KO:K05415]
102408845  TLR8; toll-like receptor 8 isoform X1 [KO:K10170]
102409386  TLR7; toll-like receptor 7 isoform X1 [KO:K05404]
102409559  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
102409665  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102410468  [KO:K05402]
102412626  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102412929  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102412933  CXCL8; interleukin-8 precursor [KO:K10030]
102413537  [KO:K05408]
102413796  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102414149  TLR9; toll-like receptor 9 isoform X2 [KO:K10161]
102414314  STAT2; signal transducer and activator of transcription 2 isoform X2 [KO:K11221]
102414434  [KO:K05414]
102414674  CXCL11; C-X-C motif chemokine 11 isoform X2 [KO:K12672]
102414734  [KO:K12964]
102415013  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102415065  CCL3; C-C motif chemokine 3 precursor [KO:K05408]
102415101  IL6; interleukin-6 isoform X1 [KO:K05405]
102415109  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102415113  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X4 [KO:K04427] [EC:2.7.11.25]
102415114  [KO:K05414]
102415351  CXCL9; C-X-C motif chemokine 9 [KO:K05416]
102415400  [KO:K05408]
102415422  LBP; lipopolysaccharide-binding protein precursor [KO:K05399]
102415500  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X2 [KO:K11220]
102415727  [KO:K05408]
102416204  [KO:K05414]
112577604  TLR1; toll-like receptor 1 [KO:K05398]
112577611  [KO:K05408]
112577736  [KO:K05414]
112583541  [KO:K05414]
112583544  [KO:K05414]
112583545  [KO:K05414]
112583546  [KO:K05414]
112583548  [KO:K05414]
112583867  [KO:K05414]
112583876  [KO:K05414]
112583880  [KO:K05414]
112583883  [KO:K05415]
112583884  [KO:K05415]
112583885  [KO:K05415]
112583886  [KO:K05415]
123332785  [KO:K05415]
123465262  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
123465588  [KO:K05415]
123465589  [KO:K05415]
Reference
PMID:17275323
  Authors
Kawai T, Akira S.
  Title
TLR signaling.
  Journal
Semin Immunol 19:24-32 (2007)
DOI:10.1016/j.smim.2006.12.004
Reference
PMID:17457343
  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
PMID:16932750
  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
PMID:17395581
  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
PMID:16497588
  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
PMID:14698224
  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
PMID:12734364
  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
PMID:14751764
  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
PMID:17637696
  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
PMID:17507094
  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
PMID:11101877
  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
PMID:16924467
  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
bbub04010  MAPK signaling pathway
bbub04060  Cytokine-cytokine receptor interaction
bbub04064  NF-kappa B signaling pathway
bbub04120  Ubiquitin mediated proteolysis
bbub04151  PI3K-Akt signaling pathway
bbub04210  Apoptosis
bbub04610  Complement and coagulation cascades
bbub04630  JAK-STAT signaling pathway
KO pathway
ko04620   

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