KEGG   PATHWAY: mmu04620
Entry
mmu04620                    Pathway                                

Name
Toll-like receptor signaling pathway - Mus musculus (mouse)
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
mmu04620  Toll-like receptor signaling pathway
mmu04620

Organism
Mus musculus (mouse) [GN:mmu]
Gene
21897  Tlr1; toll-like receptor 1 [KO:K05398]
24088  Tlr2; toll-like receptor 2 [KO:K10159]
21899  Tlr6; toll-like receptor 6 [KO:K10169]
16803  Lbp; lipopolysaccharide binding protein [KO:K05399]
12475  Cd14; CD14 antigen [KO:K04391]
17087  Ly96; lymphocyte antigen 96 [KO:K05400]
142980  Tlr3; toll-like receptor 3 [KO:K05401]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
53791  Tlr5; toll-like receptor 5 [KO:K10168]
170743  Tlr7; toll-like receptor 7 [KO:K05404]
170744  Tlr8; toll-like receptor 8 [KO:K10170]
13038  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
81897  Tlr9; toll-like receptor 9 [KO:K10161]
19353  Rac1; Rac family small GTPase 1 [KO:K04392]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
54473  Tollip; toll interacting protein [KO:K05402]
17874  Myd88; myeloid differentiation primary response gene 88 [KO:K04729]
117149  Tirap; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein [KO:K05403]
14082  Fadd; Fas (TNFRSF6)-associated via death domain [KO:K02373]
12370  Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
66513  Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
26410  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
26397  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26398  Map2k4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
26400  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
16476  Jun; jun proto-oncogene [KO:K04448]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
21926  Tnf; tumor necrosis factor [KO:K03156]
16176  Il1b; interleukin 1 beta [KO:K04519]
16193  Il6; interleukin 6 [KO:K05405]
16159  Il12a; interleukin 12a [KO:K05406]
16160  Il12b; interleukin 12b [KO:K05425]
20304  Ccl5; chemokine (C-C motif) ligand 5 [KO:K12499]
20302  Ccl3; chemokine (C-C motif) ligand 3 [KO:K05408]
20303  Ccl4; chemokine (C-C motif) ligand 4 [KO:K12964]
225471  Ticam2; toll-like receptor adaptor molecule 2 [KO:K05409]
106759  Ticam1; toll-like receptor adaptor molecule 1 [KO:K05842]
19766  Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
27056  Irf5; interferon regulatory factor 5 [KO:K09446]
54123  Irf7; interferon regulatory factor 7 [KO:K09447]
20750  Spp1; secreted phosphoprotein 1 [KO:K06250]
56489  Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:2.7.11.10]
56480  Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
22031  Traf3; TNF receptor-associated factor 3 [KO:K03174]
54131  Irf3; interferon regulatory factor 3 [KO:K05411]
21939  Cd40; CD40 antigen [KO:K03160]
12519  Cd80; CD80 antigen [KO:K05412]
12524  Cd86; CD86 antigen [KO:K05413]
15962  Ifna1; interferon alpha 1 [KO:K05414]
15965  Ifna2; interferon alpha 2 [KO:K05414]
15967  Ifna4; interferon alpha 4 [KO:K05414]
15968  Ifna5; interferon alpha 5 [KO:K05414]
15969  Ifna6; interferon alpha 6 [KO:K05414]
15970  Ifna7; interferon alpha 7 [KO:K05414]
15972  Ifna9; interferon alpha 9 [KO:K05414]
15964  Ifna11; interferon alpha 11 [KO:K05414]
242519  Ifna12; interferon alpha 12 [KO:K05414]
230396  Ifna13; interferon alpha 13 [KO:K05414]
404549  Ifna14; interferon alpha 14 [KO:K05414]
15974  Ifnab; interferon alpha B [KO:K05414]
242517  Ifna15; interferon alpha 15 [KO:K05414]
230398  Ifna16; interferon alpha 16 [KO:K05414]
15977  Ifnb1; interferon beta 1, fibroblast [KO:K05415]
15975  Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]
15976  Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
15945  Cxcl10; chemokine (C-X-C motif) ligand 10 [KO:K12671]
17329  Cxcl9; chemokine (C-X-C motif) ligand 9 [KO:K05416]
56066  Cxcl11; chemokine (C-X-C motif) ligand 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
mmu04010  MAPK signaling pathway
mmu04060  Cytokine-cytokine receptor interaction
mmu04064  NF-kappa B signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04151  PI3K-Akt signaling pathway
mmu04210  Apoptosis
mmu04610  Complement and coagulation cascades
mmu04630  JAK-STAT signaling pathway
KO pathway
ko04620   

DBGET integrated database retrieval system