KEGG PATHWAY: rno04620

PATHWAY: rno04620

Entry

rno04620 Pathway

Name

Toll-like receptor signaling pathway - Rattus norvegicus (rat)

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

rno04620

Toll-like receptor signaling pathway

Organism

Rattus norvegicus (rat) [GN:rno]

Gene

305354	Tlr1; toll-like receptor 1 [KO:K05398]
310553	Tlr2; toll-like receptor 2 [KO:K10159]
305353	Tlr6; toll-like receptor 6 [KO:K10169]
29469	Lbp; lipopolysaccharide binding protein [KO:K05399]
60350	Cd14; CD14 molecule [KO:K04391]
448830	Ly96; lymphocyte antigen 96 [KO:K05400]
364594	Tlr3; toll-like receptor 3 [KO:K05401]
29260	Tlr4; toll-like receptor 4 [KO:K10160]
289337	Tlr5; toll-like receptor 5 [KO:K10168]
317468	Tlr7; toll-like receptor 7 [KO:K05404]
684440	Tlr8; toll-like receptor 8 [KO:K10170]
29175	Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
338457	Tlr9; toll-like receptor 9 [KO:K10161]
363875	Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
85243	Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
170911	Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
366508	Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
298947	Pik3cg; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
25513	Pik3r1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
60664	Pik3r3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
29741	Pik3r2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
497931	Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
24185	Akt1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
25233	Akt2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
29414	Akt3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
361677	Tollip; toll interacting protein [KO:K05402]
301059	Myd88; myeloid differentiation primary response 88 [KO:K04729]
680127	Tirap; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein [KO:K05403]
266610	Fadd; Fas (TNFRSF6)-associated via death domain [KO:K02373]
64044	Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
300177	Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
363520	Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
311245	Traf6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
315139	Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
308267	Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
313121	Map3k7; mitogen activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100910771	mitogen-activated protein kinase kinase kinase 7-like; K04427 mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] [KO:K04427] [EC:2.7.11.25]
309295	Ikbkg; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
309361	Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
84351	Ikbkb; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
25493	Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
81736	Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
309165	Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
116596	Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
170851	Map2k1; mitogen activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960	Map2k2; mitogen activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590	Mapk1; mitogen activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689	Mapk3; mitogen activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
303200	Map2k3; mitogen activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
100911550	dual specificity mitogen-activated protein kinase kinase 3-like; K04432 mitogen-activated protein kinase kinase 3 [EC:2.7.12.2] [KO:K04432] [EC:2.7.12.2]
114495	Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
287398	Map2k4; mitogen activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
363855	Map2k7; mitogen activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
81649	Mapk14; mitogen activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352	Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513	Mapk13; mitogen activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314	Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272	Mapk10; mitogen activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
50658	Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
116554	Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516	Jun; jun proto-oncogene [KO:K04448]
314322	Fos; FBJ osteosarcoma oncogene [KO:K04379]
24835	Tnf; tumor necrosis factor [KO:K03156]
24494	Il1b; interleukin 1 beta [KO:K04519]
24498	Il6; interleukin 6 [KO:K05405]
84405	Il12a; interleukin 12A [KO:K05406]
64546	Il12b; interleukin 12B [KO:K05425]
81780	Ccl5; chemokine (C-C motif) ligand 5 [KO:K12499]
25542	Ccl3; chemokine (C-C motif) ligand 3 [KO:K05408]
116637	Ccl4; chemokine (C-C motif) ligand 4 [KO:K12964]
364867	Ticam2; toll-like receptor adaptor molecule 2 [KO:K05409]
363328	similar to TICAM-1; K05842 toll-like receptor adapter molecule 1 [KO:K05842]
306886	Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
296953	Irf5; interferon regulatory factor 5 [KO:K09446]
293624	Irf7; interferon regulatory factor 7 [KO:K09447]
25353	Spp1; secreted phosphoprotein 1 [KO:K06250]
363984	Ikbke; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon [KO:K07211] [EC:2.7.11.10]
299827	Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
362788	Traf3; Tnf receptor-associated factor 3 [KO:K03174]
292892	Irf3; interferon regulatory factor 3 [KO:K05411]
171369	Cd40; CD40 molecule, TNF receptor superfamily member 5 [KO:K03160]
25408	Cd80; Cd80 molecule [KO:K05412]
56822	Cd86; CD86 molecule [KO:K05413]
298205	Ifna4; interferon, alpha 4 [KO:K05414]
298213	Ifna2; interferon alpha family, gene 2 [KO:K05414]
298210	Ifna1; interferon-alpha 1 [KO:K05414]
298211	Ifna11; interferon alpha family, gene 11 [KO:K05414]
690894	Ifna5; interferon alpha family, gene 5 [KO:K05414]
100912314	interferon alpha-1-like; K05414 interferon alpha [KO:K05414]
24481	Ifnb1; interferon beta 1, fibroblast [KO:K05415]
288264	Ifnar1; interferon (alpha, beta and omega) receptor 1 [KO:K05130]
686326	similar to Interferon-alpha/beta receptor beta chain precursor (IFN-alpha-REC) (Type I interferon receptor) (IFN-R) (Interferon alpha/beta receptor-2); K05131 interferon receptor 2 [KO:K05131]
25124	Stat1; signal transducer and activator of transcription 1 [KO:K11220]
245920	Cxcl10; chemokine (C-X-C motif) ligand 10 [KO:K12671]
246759	Cxcl9; chemokine (C-X-C motif) ligand 9 [KO:K05416]
305236	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 (96)   
   KEGG GENES (96)   
All databases (98)   

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