Toll-like receptor signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
Zoom out 50% Move left to zoom out, right to zoom in Zoom in 50% 100%

Toll-like receptor signaling pathway - Homo sapiens (human) cluster_node73 G+ cluster_node74 !cell Exterior cluster_Membrane Membrane cluster_Endosome Endosome cluster_node75 !Flag cluster_Degradation Degradation cluster_node76 !DNA cluster_node77 !Cytokine cluster_node78 !Complement cluster_node79 !JAK cluster_node80 Inflammatory cytokines cluster_node81 Co-stimulatory molecules cluster_node82 !MyD node2 1 toll-like receptor 1 TLR1 node2->TLR1 toll-like receptor 2 TLR2 node2->TLR2 toll-like receptor 6 TLR6 node2->TLR6 node3 12 node4 5 node5 10 Lipopolysaccharide biosynthesis node8 MD-2 Lipopolysaccharide biosynthesis->node8 toll-like receptor 4 TLR4 node8->TLR4 ras-related C3 botulinum toxin substrate 1 (rho family,small GTP binding protein Rac1) RAC1 P13K RAC1->P13K node10 TOLLIP MYD88 TIRAP Fas (TNFRSF6)-associated via death domain FADD node10->FADD node20 IRAK4 IRAK1 node10->node20 node11 TIRAP MYD88 node11->FADD node11->node20 TRAM TRIF TRAM->TRIF myeloid differentiation primary response gene (88) MYD88 MYD88->node20 node12 4 P13K->node12 P13K AKT P13K->AKT node13 29 AKT->node13 AKT node17 NF-kB AKT->node17 node14 2 node14->RAC1 node14->node10 node15 3 node15->RAC1 node15->node10 node16 30 node17->node16 NF-kB IkBalpha node17->IkBalpha DNA node17->DNA MyD88 2 MyD88 2->node20 interleukin-1 receptor-associated kinase 4 IRAK4 MyD88 2->IRAK4 node18 Imidazoquinolin (anti-viral compounds) node9 TLR7/8 node18->node9 ssRNA ssRNA->node9 Unmethylated CpG DNA toll-like receptor 9 TLR9 Unmethylated CpG DNA->TLR9 dsRNA toll-like receptor 3 TLR3 dsRNA->TLR3 caspase 8,apoptosis-related cysteine peptidase CASP8 FADD->CASP8 node19 6 CASP8->node19 CASP8 Apoptosis CASP8->Apoptosis TNF receptor-associated factor 6 TRAF6 node20->TRAF6 node21 3 TRAF6->node21 TRAF6 node22 TAB1 TAB2 TAK1 TRAF6->node22 interferon regulatory factor 5 IRF5 TRAF6->IRF5 node25 IKBKG CHUK IKBKB node22->node25 +p node28 MKK3/6 node22->node28 +p node29 MKK4/7 node22->node29 +p node23 4 IkBalpha->node23 IkBalpha Ubiquitin mediated proteolysis IkBalpha->Ubiquitin mediated proteolysis node24 5 node25->IkBalpha +p node25->node24 IKBKG~CHUK~IKBKB p105 node25->p105 node26 3 node27 TRAF6 RIPK1 node27->node22 node27->node26 TRAF6~RIPK1 p38 node28->p38 +p JNK node29->JNK +p node30 2 p38->node30 p38 node37 AP-1 p38->node37 node31 24 ERK ERK->node31 ERK ERK->node37 node32 2 node33 MEK1/2 node33->ERK +p node33->node32 MEK1/2 node34 29 p105->node34 p105 Tpl2 p105->Tpl2 p105->Ubiquitin mediated proteolysis Tpl2->node33 +p Tpl2->Ubiquitin mediated proteolysis node35 11 JNK->node35 JNK JNK->node37 +p node36 1 node37->node36 AP-1 DNA 2 node37->DNA 2 DNA 3 IRF5->DNA 3 node38 21 node39 3 node41 10 node43 3 node45 4 Proinflammatory effects node50 4 node44 IL-12 node50->node44 node40 IL-1beta node50->node40 node42 IL-6 node50->node42 TNFalpha node50->TNFalpha node51 5 node46 IL-8 node51->node46 node47 MIP-1alpha node51->node47 node48 MIP-1beta node51->node48 RANTES node51->RANTES node52 3 TRAF6 2 TRAF6 2->IRF5 TRAF6 2->node52 TRAF6 2 interferon regulatory factor 7 IRF7 TRAF6 2->IRF7 node53 1 IRAK4->TRAF6 2 +p IRAK4->node53 IRAK4 interleukin-1 receptor-associated kinase 1 IRAK1 IRAK4->IRAK1 +p node54 2 IRAK1->node54 IRAK1 IRAK1->IRF7 +p DNA 4 IRF7->DNA 4 node57 6 node55 IFN-alpha node57->node55 node56 IFN-beta node57->node56 IKKalpha IKKalpha->IRF7 +p TNF receptor-associated factor 3 TRAF3 node59 IKBKE TBK1 TRAF3->node59 node58 1 node59->IRF7 +p node59->node58 IKBKE~TBK1 interferon regulatory factor 3 IRF3 node59->IRF3 +p node60 4 OPN OPN->IRF7 OPN->node60 OPN DNA 5 IRF3->DNA 5 node62 1 node63 1 node64 7 CD40 molecule,TNF receptor superfamily member 5 CD40 node64->CD40 CD80 molecule CD80 node64->CD80 CD86 molecule CD86 node64->CD86 node65 IP-10 node69 Chemotactic effects (T-Cell) node65->node69 MIG MIG->node69 node66 J-TAC node66->node69 node67 8 node67->node65 node67->MIG node67->node66 node68 T-Cell Stimulation TLR1->node14 TLR2->node3 TLR2 TLR2->node14 TLR2->node15 TLR6->node15 node44->node43 IL-12 node44->Proinflammatory effects node40->node39 IL-1beta node40->Proinflammatory effects node42->node41 IL-6 node42->Proinflammatory effects TNFalpha->node38 TNFalpha TNFalpha->Proinflammatory effects node46->node45 IL-8 node49 Chemotactic effects (Neutrophil, Immature DC, NK Cell) node46->node49 node47->node49 node48->node49 RANTES->node49 Antiviral effects node55->Antiviral effects node56->Antiviral effects node61 IFN-beta 2 node56->node61 Autocrine / Paracrine CD40->node68 CD80->node68 CD86->node63 CD86 CD86->node68 DNA 2->node50 CD14 molecule CD14 CD14->node4 CD14 CD14->TLR4 TLR4->node5 TLR4 TLR4->node11 TLR4->TRAM DNA->node50 DNA 3->node51 DNA 4->node57 DNA 5->node57 DNA 5->node64 DNA 5->node67 DNA 6 DNA 6->node67 Flagellin toll-like receptor 5 TLR5 Flagellin->TLR5 TLR5->MYD88 node6 IFN-aBR signal transducer and activator of transcription 1,91kDa STAT1 node6->STAT1 STAT1->node62 STAT1 STAT1->DNA 6 JAK-STAT pathway node61->node6 node9->MyD88 2 node7 LPS (G-) node7->CD14 Lipoarabinomannan Lipoarabinomannan->node2 Lipoprotein Lipoprotein->node2 node1 Peptidoglycan (G+) node1->node2 TLR3->TRIF TRIF->node27 TRIF->TRAF3 TLR9->MyD88 2 Zymosan Zymosan->node2 cathepsin K CTSK Flagellar Assembly node70 Cytokine -cytokine receptor interaction - Homo sapiens Complement and Coagulation Cascade node71 Jak -STAT signaling pathway - Homo sapiens lipopolysaccharide binding protein LBP node72 MYD88-independent pathway print "