KEGG PATHWAY: xtr04620

KEGG

PATHWAY: xtr04620

Entry

xtr04620                    Pathway

Name

Toll-like receptor signaling pathway - Xenopus tropicalis (tropical clawed frog)

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

Xenopus tropicalis (tropical clawed frog) [GN:xtr]

Gene

tlr1; toll-like receptor 1 [KO:K05398]

toll-like receptor 1 [KO:K05398]

tlr2; toll-like receptor 2 type-2 [KO:K10159]

toll-like receptor 2 type-2 [KO:K10159]

toll-like receptor 2 [KO:K10159]

toll-like receptor 2 [KO:K10159]

toll-like receptor 2 [KO:K10159]

tlr6; toll-like receptor 1 [KO:K10169]

tlr3; toll-like receptor 3 [KO:K05401]

toll-like receptor 5 [KO:K10168]

toll-like receptor 5 [KO:K10168]

tlr7; toll-like receptor 7 [KO:K05404]

tlr9; toll-like receptor 7 [KO:K05404]

tlr8; toll-like receptor 8 [KO:K10170]

toll-like receptor 8 [KO:K10170]

ctsk; cathepsin K (pycnodysostosis) precursor [KO:K01371] [EC:3.4.22.38]

ctsk; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]

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

cathepsin S [KO:K01371] [EC:3.4.22.38]

rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]

pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]

pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]

pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]

pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]

pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]

akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]

akt1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]

tollip; toll-interacting protein [KO:K05402]

myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]

tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]

uncharacterized protein LOC100491693 isoform X1 [KO:K05403]

fadd; FAS-associated death domain protein [KO:K02373]

casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]

irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]

irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]

traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]

tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]

tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]

map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]

ikbkg; NF-kappa-B essential modulator [KO:K07210]

chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]

ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]

nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]

nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]

rela; transcription factor p65 [KO:K04735]

map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]

map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]

map2k4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]

map2k7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]

mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]

mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]

mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]

mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]

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

mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]

mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]

jun; transcription factor AP-1 [KO:K04448]

fos; proto-oncogene c-Fos [KO:K04379]

tnf; tumor necrosis factor [KO:K03156]

il1b; interleukin-1 beta [KO:K04519]

uncharacterized protein LOC116409784 isoform X1 [KO:K04519]

il6; interleukin-6 [KO:K05405]

interleukin-12 subunit alpha [KO:K05406]

interleukin-12 subunit beta [KO:K05425]

il12b; interleukin-12 subunit beta isoform X1 [KO:K05425]

interleukin-8 [KO:K10030]

cxcl8; interleukin-8 [KO:K10030]

cxcl2; interleukin-8 [KO:K10030]

interleukin-8 [KO:K10030]

interleukin-8 [KO:K10030]

ccl5; C-C motif chemokine 5 isoform X3 [KO:K12499]

uncharacterized protein LOC101730633 [KO:K05408]

ccl4; C-C motif chemokine 4 homolog [KO:K12964]

C-C motif chemokine 4 homolog [KO:K12964]

TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]

ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]

irf5; interferon regulatory factor 5 [KO:K09446]

irf7; interferon regulatory factor 7 [KO:K09447]

ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]

tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]

traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]

irf3; interferon regulatory factor 3 [KO:K05411]

cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]

cd80; T-lymphocyte activation antigen CD80 [KO:K05412]

cd86; T-lymphocyte activation antigen CD86 [KO:K05413]

interferon beta [KO:K05414]

interferon omega-1-like [KO:K05414]

interferon alpha-3-like [KO:K05414]

ifnar1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]

ifnar2.1; interferon (alpha, beta and omega) receptor 2, gene 1 precursor [KO:K05131]

ifnar2.2; interferon alpha/beta receptor 2 [KO:K05131]

jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]

tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]

stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]

stat2; signal transducer and activator of transcription 2 [KO:K11221]

irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]

cxcl9; C-X-C motif chemokine 11-1 [KO:K12671]

cxcl10; C-X-C motif chemokine 10 [KO:K12671]

cxcl11; C-X-C motif chemokine 11-1 [KO:K12671]

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

Ubiquitin mediated proteolysis

Apoptosis

KO pathway

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