KEGG PATHWAY: mmu04620

KEGG

PATHWAY: mmu04620

Entry

mmu04620                    Pathway

Name

Toll-like receptor signaling pathway - Mus musculus (house 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

Toll-like receptor signaling pathway

Organism

Mus musculus (house mouse) [GN:mmu]

Gene

Ticam1; TIR domain containing adaptor molecule 1 [KO:K05842]

Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]

Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]

Tirap; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein [KO:K05403]

Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]

Cd14; CD14 antigen [KO:K04391]

Cd80; CD80 antigen [KO:K05412]

Cd86; CD86 antigen [KO:K05413]

Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]

Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]

Fadd; Fas associated via death domain [KO:K02373]

Fos; FBJ osteosarcoma oncogene [KO:K04379]

Tlr3; toll-like receptor 3 [KO:K05401]

Cxcl10; C-X-C motif chemokine ligand 10 [KO:K12671]

Ifna1; interferon alpha 1 [KO:K05414]

Ifna11; interferon alpha 11 [KO:K05414]

Ifna2; interferon alpha 2 [KO:K05414]

Ifna4; interferon alpha 4 [KO:K05414]

Ifna5; interferon alpha 5 [KO:K05414]

Ifna6; interferon alpha 6 [KO:K05414]

Ifna7; interferon alpha 7 [KO:K05414]

Ifna9; interferon alpha 9 [KO:K05414]

Ifnab; interferon alpha B [KO:K05414]

Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]

Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]

Ifnb1; interferon beta 1, fibroblast [KO:K05415]

Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]

Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]

Il12a; interleukin 12a [KO:K05406]

Il12b; interleukin 12b [KO:K05425]

Il1b; interleukin 1 beta [KO:K04519]

Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]

Il6; interleukin 6 [KO:K05405]

Irf9; interferon regulatory factor 9 [KO:K04693]

Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]

Jun; jun proto-oncogene [KO:K04448]

Lbp; lipopolysaccharide binding protein [KO:K05399]

Tlr7; toll-like receptor 7 [KO:K05404]

Tlr8; toll-like receptor 8 [KO:K10170]

Ly96; lymphocyte antigen 96 [KO:K05400]

Cxcl9; C-X-C motif chemokine ligand 9 [KO:K05416]

Myd88; myeloid differentiation primary response gene 88 [KO:K04729]

Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]

Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]

Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]

Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]

Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]

Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]

Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]

Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]

Rac1; Rac family small GTPase 1 [KO:K04392]

Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]

Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]

Ccl3; C-C motif chemokine ligand 3 [KO:K05408]

Ccl4; C-C motif chemokine ligand 4 [KO:K12964]

Ccl5; C-C motif chemokine ligand 5 [KO:K12499]

Spp1; secreted phosphoprotein 1 [KO:K06250]

Stat1; signal transducer and activator of transcription 1 [KO:K11220]

Stat2; signal transducer and activator of transcription 2 [KO:K11221]

Tlr1; toll-like receptor 1 [KO:K05398]

Tlr4; toll-like receptor 4 [KO:K10160]

Tlr6; toll-like receptor 6 [KO:K10169]

Tnf; tumor necrosis factor [KO:K03156]

Cd40; CD40 antigen [KO:K03160]

Traf3; TNF receptor-associated factor 3 [KO:K03174]

Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]

Ticam2; TIR domain containing adaptor molecule 2 [KO:K05409]

Ifna13; interferon alpha 13 [KO:K05414]

Ifna16; interferon alpha 16 [KO:K05414]

Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]

Tlr2; toll-like receptor 2 [KO:K10159]

Ifna15; interferon alpha 15 [KO:K05414]

Ifna12; interferon alpha 12 [KO:K05414]

Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]

Map2k4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]

Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]

Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]

Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]

Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]

Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]

Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]

Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]

Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]

Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]

Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]

Irf5; interferon regulatory factor 5 [KO:K09446]

Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]

Ifna14; interferon alpha 14 [KO:K05414]

Tlr5; toll-like receptor 5 [KO:K10168]

Irf7; interferon regulatory factor 7 [KO:K09447]

Irf3; interferon regulatory factor 3 [KO:K05411]

Tollip; toll interacting protein [KO:K05402]

Tyk2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]

Cxcl11; chemokine (C-X-C motif) ligand 11 [KO:K12672]

Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]

Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:2.7.11.10]

Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]

Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]

Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]

Tlr9; toll-like receptor 9 [KO:K10161]

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

MAPK signaling pathway

Cytokine-cytokine receptor interaction

NF-kappa B signaling pathway

Ubiquitin mediated proteolysis

PI3K-Akt signaling pathway

Apoptosis

Complement and coagulation cascades

JAK-STAT signaling pathway

KO pathway

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