KEGG PATHWAY: ko04620

PATHWAY: ko04620

Entry

ko04620                     Pathway

Name

Toll-like receptor signaling pathway

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

ko04620

Toll-like receptor signaling pathway

Orthology

K05398

toll-like receptor 1

K10159

toll-like receptor 2

K10169

toll-like receptor 6

K05399

lipopolysaccharide-binding protein

K04391

monocyte differentiation antigen CD14

K05400

lymphocyte antigen 96

K05401

toll-like receptor 3

K10160

toll-like receptor 4

K10168

toll-like receptor 5

K05404

toll-like receptor 7

K10170

toll-like receptor 8

K01371

cathepsin K [EC:3.4.22.38]

K10161

toll-like receptor 9

K04392

Ras-related C3 botulinum toxin substrate 1

K00922

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02649

phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K04456

RAC serine/threonine-protein kinase [EC:2.7.11.1]

K05402

toll-interacting protein

K04729

myeloid differentiation primary response protein MyD88

K05403

toll-interleukin 1 receptor (TIR) domain-containing adaptor protein

K02373

FAS-associated death domain protein

K04398

caspase 8 [EC:3.4.22.61]

K04733

interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]

K04730

interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]

K03175

TNF receptor-associated factor 6 [EC:2.3.2.27]

K04403

TAK1-binding protein 1

K04404

TAK1-binding protein 2

K04427

mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]

K07210

inhibitor of nuclear factor kappa-B kinase subunit gamma

K04467

inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]

K07209

inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]

K04734

NF-kappa-B inhibitor alpha

K02580

nuclear factor NF-kappa-B p105 subunit

K04735

transcription factor p65

K04415

mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25]

K04368

mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04432

mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]

K04433

mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]

K04430

mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]

K04431

mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]

K04441

p38 MAP kinase [EC:2.7.11.24]

K04440

mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04448

transcription factor AP-1

K04379

proto-oncogene protein c-fos

K03156

tumor necrosis factor superfamily, member 2

K04519

interleukin 1 beta

K05405

interleukin 6

K05406

interleukin 12A

K05425

interleukin 12B

K10030

interleukin 8

K12499

C-C motif chemokine 5

K05408

C-C motif chemokine 3

K12964

C-C motif chemokine 4

K05409

TRIF-related adaptor molecule

K05842

toll-like receptor adapter molecule 1

K02861

receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]

K09446

interferon regulatory factor 5

K09447

interferon regulatory factor 7

K06250

secreted phosphoprotein 1

K07211

inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]

K05410

TANK-binding kinase 1 [EC:2.7.11.10]

K03174

TNF receptor-associated factor 3

K05411

interferon regulatory factor 3

K03160

tumor necrosis factor receptor superfamily member 5

K05412

CD80 antigen

K05413

CD86 antigen

K05414

interferon alpha

K05415

interferon beta

K05130

interferon receptor 1

K05131

interferon receptor 2

K11217

Janus kinase 1 [EC:2.7.10.2]

K11219

non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]

K11220

signal transducer and activator of transcription 1

K11221

signal transducer and activator of transcription 2

K04693

interferon regulatory factor 9

K12671

C-X-C motif chemokine 10

K05416

C-X-C motif chemokine 9

K12672

C-X-C motif chemokine 11

Reference

PMID:17275323

Authors

Kawai T, Akira S.

Title

TLR signaling.

Journal

Semin Immunol 19:24-32 (2007)
DOI:10.1016/j.smim.2006.12.004

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)
DOI:10.1038/nri2079

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)
DOI:10.1038/nri1900

Reference

PMID:17395581

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

PMID:16497588

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

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)
DOI:10.1016/j.molimm.2003.10.006

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)
DOI:10.4049/jimmunol.170.10.5165

Reference

PMID:14751764

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

PMID:17637696

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

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)
DOI:10.1016/j.molimm.2007.04.002

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)
DOI:10.1038/82797

Reference

PMID:16924467

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

ko00540

Lipopolysaccharide biosynthesis

ko02040

Flagellar assembly

ko04010

MAPK signaling pathway

ko04060

Cytokine-cytokine receptor interaction

ko04064

NF-kappa B signaling pathway

ko04120

Ubiquitin mediated proteolysis

ko04151

PI3K-Akt signaling pathway

ko04210

Apoptosis

ko04610

Complement and coagulation cascades

ko04630

JAK-STAT signaling pathway

All links

Gene (80)   
   KEGG ORTHOLOGY (80)   
All databases (80)   

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