KEGG PATHWAY: pcad04620

KEGG

PATHWAY: pcad04620

Entry

pcad04620                   Pathway

Name

Toll-like receptor signaling pathway - Physeter macrocephalus (sperm whale)

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

Physeter macrocephalus (sperm whale) [GN:pcad]

Gene

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

MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]

RELA; transcription factor p65 isoform X1 [KO:K04735]

TRAF3; TNF receptor-associated factor 3 [KO:K03174]

SPP1; osteopontin [KO:K06250]

JUN; transcription factor Jun [KO:K04448]

PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]

CCL5; C-C motif chemokine 5 [KO:K12499]

CD80; T-lymphocyte activation antigen CD80 isoform X2 [KO:K05412]

TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]

TLR2; toll-like receptor 2 [KO:K10159]

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

AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]

PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]

CXCL9; C-X-C motif chemokine 9 [KO:K05416]

MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]

MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]

STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]

CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]

MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]

MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X3 [KO:K04432] [EC:2.7.12.2]

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

PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]

CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]

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

TLR6; toll-like receptor 6 [KO:K10169]

CXCL8; interleukin-8 [KO:K10030]

IL6; interleukin-6 [KO:K05405]

CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]

TOLLIP; toll-interacting protein [KO:K05402]

IL12B; interleukin-12 subunit beta [KO:K05425]

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

NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]

AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]

STAT2; signal transducer and activator of transcription 2 [KO:K11221]

LBP; lipopolysaccharide-binding protein [KO:K05399]

MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]

IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]

IL12A; interleukin-12 subunit alpha [KO:K05406]

FOS; protein c-Fos [KO:K04379]

TLR1; toll-like receptor 1 [KO:K05398]

TNF; tumor necrosis factor [KO:K03156]

TLR4; toll-like receptor 4 isoform X1 [KO:K10160]

TLR5; toll-like receptor 5 [KO:K10168]

TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]

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]

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

RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]

PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]

IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]

CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]

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

TICAM2; TIR domain-containing adapter molecule 2 isoform X1 [KO:K05409]

MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]

MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]

IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]

[KO:K04456] [EC:2.7.11.1]

IFNB1; interferon beta [KO:K05415]

RAC1; ras-related C3 botulinum toxin substrate 1 isoform X2 [KO:K04392]

MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]

CD14; monocyte differentiation antigen CD14 [KO:K04391]

TLR7; toll-like receptor 7 isoform X1 [KO:K05404]

IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]

PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]

TLR8; toll-like receptor 8 [KO:K10170]

MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431] [EC:2.7.12.2]

PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]

LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]

TRAF6; TNF receptor-associated factor 6 isoform X2 [KO:K03175] [EC:2.3.2.27]

CXCL10; C-X-C motif chemokine 10 [KO:K12671]

CXCL11; C-X-C motif chemokine 11 isoform X2 [KO:K12672]

MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]

MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

IL1B; interleukin-1 beta [KO:K04519]

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 isoform X1 [KO:K05410] [EC:2.7.11.10]

IRF5; interferon regulatory factor 5 isoform X2 [KO:K09446]

MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]

MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]

IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]

TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]

IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]

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

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NF-kappa B signaling pathway

Ubiquitin mediated proteolysis

PI3K-Akt signaling pathway

Apoptosis

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JAK-STAT signaling pathway

KO pathway

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