Entry 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 systemBRITE hierarchy
Pathway map ko04620 Toll-like receptor signaling pathway
Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02373 FADD; FAS-associated death domain protein
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02861 RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1 ]
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03160 TNFRSF5, CD40; tumor necrosis factor receptor superfamily member 5
K03174 TRAF3; TNF receptor-associated factor 3
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04379 FOS; proto-oncogene protein c-fos
K04391 CD14; monocyte differentiation antigen CD14
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04415 MAP3K8, COT; mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 JUN; transcription factor AP-1
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04519 IL1B; interleukin 1 beta
K04693 IRF9, ISGF3G, P48; interferon regulatory factor 9
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05130 IFNAR1; interferon receptor 1
K05131 IFNAR2; interferon receptor 2
K05398 TLR1, CD281; toll-like receptor 1
K05399 LBP; lipopolysaccharide-binding protein
K05400 LY96, MD-2; lymphocyte antigen 96
K05401 TLR3, CD283; toll-like receptor 3
K05402 TOLLIP; toll-interacting protein
K05403 TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K05404 TLR7; toll-like receptor 7
K05408 CCL3; C-C motif chemokine 3
K05409 TIRP, TRAM; TRIF-related adaptor molecule
K05411 IRF3; interferon regulatory factor 3
K05416 CXCL9; C-X-C motif chemokine 9
K05842 TRIF; toll-like receptor adapter molecule 1
K06250 SPP1, BNSP, OPN; secreted phosphoprotein 1
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07211 IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K09446 IRF5; interferon regulatory factor 5
K09447 IRF7; interferon regulatory factor 7
K10030 IL8, CXCL8; interleukin 8
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K10161 TLR9, CD289; toll-like receptor 9
K10168 TLR5; toll-like receptor 5
K10169 TLR6, CD286; toll-like receptor 6
K10170 TLR8, CD288; toll-like receptor 8
K11220 STAT1; signal transducer and activator of transcription 1
K11221 STAT2; signal transducer and activator of transcription 2
K12499 CCL5; C-C motif chemokine 5
K12671 CXCL10, IP10; C-X-C motif chemokine 10
K12672 CXCL11, I-TAC; C-X-C motif chemokine 11
K12964 CCL4; C-C motif chemokine 4
Reference Authors Kawai T, Akira S.
Title TLR signaling.
Journal Reference Authors O'Neill LA, Bowie AG.
Title The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
Journal Reference Authors Honda K, Taniguchi T.
Title IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
Journal Reference Authors Uematsu S, Akira S.
Title Toll-like receptors and Type I interferons.
Journal Reference Authors Akira S, Uematsu S, Takeuchi O.
Title Pathogen recognition and innate immunity.
Journal Reference Authors Yamamoto M, Takeda K, Akira S.
Title TIR domain-containing adaptors define the specificity of TLR signaling.
Journal 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 Reference Authors Aderem A, Smith KD.
Title A systems approach to dissecting immunity and inflammation.
Journal Reference Authors Banerjee A, Gerondakis S.
Title Coordinating TLR-activated signaling pathways in cells of the immune system.
Journal 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 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 Reference Authors Uematsu S, Akira S.
Title Toll-like receptors and innate immunity.
Journal Related ko00540 Lipopolysaccharide biosynthesis
ko04060 Cytokine-cytokine receptor interaction
ko04064 NF-kappa B signaling pathway
ko04120 Ubiquitin mediated proteolysis
ko04610 Complement and coagulation cascades
