KEGG PATHWAY: mmu04620

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

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; RAS-related C3 botulinum substrate 1 [KO:K04392]
30955	Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706	Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707	Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769	Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709	Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708	Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207	Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710	Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [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]
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 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	Gm12597; predicted gene 12597 [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

PMID:17275323

Authors

Kawai T, Akira S.

Title

TLR signaling.

Journal

Semin Immunol 19:24-32 (2007)

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)

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)

Reference

PMID:17395581

Authors

Uematsu S, Akira S.

Title

Toll-like receptors and Type I interferons.

Journal

J Biol Chem 282:15319-23 (2007)

Reference

PMID:16497588

Authors

Akira S, Uematsu S, Takeuchi O.

Title

Pathogen recognition and innate immunity.

Journal

Cell 124:783-801 (2006)

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)

Reference

Authors

Matsumoto M, Oshiumi H, Seya T.

Title

[TICAM-1, an adaptor molecule that participates in Toll-like receptor-mediated type1 interferon production.] (In Japanese)

Journal

Molecular Medicine 40:194-200 (2003)

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)

Reference

PMID:14751764

Authors

Aderem A, Smith KD.

Title

A systems approach to dissecting immunity and inflammation.

Journal

Semin Immunol 16:55-67 (2004)

Reference

PMID:17637696

Authors

Banerjee A, Gerondakis S.

Title

Coordinating TLR-activated signaling pathways in cells of the immune system.

Journal

Immunol Cell Biol : (2007)

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)

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)

Reference

PMID:16924467

Authors

Uematsu S, Akira S.

Title

Toll-like receptors and innate immunity.

Journal

J Mol Med 84:712-25 (2006)

KO pathway

ko04620

All links

Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (101)   
   KEGG GENES (101)   
All databases (103)   

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