_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e3
_enti_e2
default_fact_i1
_enti_e55
default_fact_i3
default_fact_i2
_enti_e53
_enti_e59
_enti_e56
_enti_e54
_enti_e52
_enti_e50
_enti_e51
_enti_e57
_enti_e58
_enti_e61
_enti_e60
_enti_e62
g2_fact_g2
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g1
g1_fact_g3
p1_propro_p1
PMID: 15950447
TLR4 recognizes bacterial LPS.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 15950447
TLR3 recognizes viral dsRNA.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 15950447
Structures and ligands for Toll-like receptors. TLR2, in collaboration with TLR1 or TLR6, discriminates between the molecular structures of triacyl and diacyl lipopeptides, respectively.
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 15950447
Structures and ligands for Toll-like receptors. TLR2, in collaboration with TLR1 or TLR6, discriminates between the molecular structures of triacyl and diacyl lipopeptides, respectively.
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 15950447, 12524386
All TLRs possess amino-terminal leucine-rich repeats, which are responsible for the recognition of PAMPs, and also possess a carboxy-terminal Tollinterleukin-1 (IL-1) receptor (TIR) domain, which is required for initiating intracellular signaling.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 15950447
TLR5 recognizes bacterial flagellin.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 15950447
TLR11 recognizes uropathigenic bacteria products.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 15950447
TLR9 recognizes bacterial and viral CpG DNA motifs.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 15950447
TLR9 also recognizes non-nucleic acids, such as hemozoin.
c25 cso30:c:InputProcess connector
c26 cso30:c:InputProcess connector
c27 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 15950447
TLR3, TLR7, TLR8 and TLR9 reside in endosomal compartments and recognize nucleic acids; TLR3 recognizes viral dsRNA, whereas TLR7 and TLR8 recognize viral ssRNA.
c28 cso30:c:InputProcess connector
c30 cso30:c:InputProcess connector
c33 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 15950447
TLR3, TLR7, TLR8 and TLR9 reside in endosomal compartments and recognize nucleic acids; TLR3 recognizes viral dsRNA, whereas TLR7 and TLR8 recognize viral ssRNA.
c29 cso30:c:InputProcess connector
c31 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 15950447, 12524386, 10549626
TLR2 recognizes peptidoglycan, in addition to the lipoproteins and lipopeptides of Gram-positive bacteria and mycoplasma lipopeptide.
c34 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 15950447, 12524386, 10549626
TLR2 recognizes peptidoglycan, in addition to the lipoproteins and lipopeptides of Gram-positive bacteria and mycoplasma lipopeptide.
c37 cso30:c:InputProcess connector
c38 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 15950447, 12524386, 10549626
TLR2 recognizes peptidoglycan, in addition to the lipoproteins and lipopeptides of Gram-positive bacteria and mycoplasma lipopeptide.
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 15950447, 12719479
Innate immune responses against zymosan, a cell-wall preparation of yeast, are mediated by the collaborative recognition of TLR2 and dectin-1, a lectin family of receptors for beta-glucans.
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p16_propro_p16
PMIID: 15950447, 15690042
CD36, a class II scavenger receptor expressed on the surface of innate immune cells, is involved in sensing some, but not all, TLR2 ligands.
c47 cso30:c:InputProcess connector
c48 cso30:c:InputProcess connector
c49 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 15950447
Signaling through dectin-1 enhanced the TLR2-mediated transcription of target genes.
c51 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 15950447, 12032557
TLR8 is a close relative of TLR7, and a transfection study has demonstrated that human, but not mouse, TLR8 confers responsiveness to resiquimod.
c53 cso30:c:InputProcess connector
c52 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 15950447
Synthetic imidazoquinoline-like molecules imiquimod (R-837) and resiquimod (R-848), and guanosine analogs such as loxoribine, have potent antiviral activities and are currently used for treating viral infections.
PMID: 15950447
Taken together, these findings indicate that mouse TLR7, human TLR7 and human TLR8 mediate the recognition of these molecules.
c55 cso30:c:InputProcess connector
c57 cso30:c:InputProcess connector
c56 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 15950447
Synthetic imidazoquinoline-like molecules imiquimod (R-837) and resiquimod (R-848), and guanosine analogs such as loxoribine, have potent antiviral activities and are currently used for treating viral infections.
PMID: 15950447
Taken together, these findings indicate that mouse TLR7, human TLR7 and human TLR8 mediate the recognition of these molecules.
c58 cso30:c:InputProcess connector
c59 cso30:c:InputProcess connector
c60 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 15950447
Synthetic imidazoquinoline-like molecules imiquimod (R-837) and resiquimod (R-848), and guanosine analogs such as loxoribine, have potent antiviral activities and are currently used for treating viral infections.
PMID: 15950447
Taken together, these findings indicate that mouse TLR7, human TLR7 and human TLR8 mediate the recognition of these molecules.
c61 cso30:c:InputProcess connector
c62 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 15950447
Synthetic imidazoquinoline-like molecules imiquimod (R-837) and resiquimod (R-848), and guanosine analogs such as loxoribine, have potent antiviral activities and are currently used for treating viral infections.
PMID: 15950447
Taken together, these findings indicate that mouse TLR7, human TLR7 and human TLR8 mediate the recognition of these molecules.
c64 cso30:c:InputProcess connector
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 15950447
Synthetic imidazoquinoline-like molecules imiquimod (R-837) and resiquimod (R-848), and guanosine analogs such as loxoribine, have potent antiviral activities and are currently used for treating viral infections.
PMID: 15950447
Taken together, these findings indicate that mouse TLR7, human TLR7 and human TLR8 mediate the recognition of these molecules.
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 15950447, 15558055
TLR3 also mediates the recognition of West Nile virus (WNV).
c69 cso30:c:InputProcess connector
c71 cso30:c:InputProcess connector
c70 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 15950447
MyD88 is utilized by all TLRs, with the exception of TLR3.
c72 cso30:c:InputProcess connector
c73 cso30:c:InputProcess connector
c74 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 15950447
The association of TLRs and MyD88 recruits members of the IL-1 receptor-associated kinase (IRAK) family; two members, IRAK4 and IRAK1, are sequentially phosphorylated, causing them to dissociate from the receptor complex, and then associate with TRAF6.
c75 cso30:c:InputProcess connector
c76 cso30:c:InputProcess connector
c78 cso30:c:InputProcess connector
c77 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 15950447
The association of TLRs and MyD88 recruits members of the IL-1 receptor-associated kinase (IRAK) family; two members, IRAK4 and IRAK1, are sequentially phosphorylated, causing them to dissociate from the receptor complex, and then associate with TRAF6.
c79 cso30:c:InputProcess connector
c80 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 15950447
The association of TLRs and MyD88 recruits members of the IL-1 receptor-associated kinase (IRAK) family; two members, IRAK4 and IRAK1, are sequentially phosphorylated, causing them to dissociate from the receptor complex, and then associate with TRAF6.
c81 cso30:c:InputProcess connector
c82 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 15950447
The association of TLRs and MyD88 recruits members of the IL-1 receptor-associated kinase (IRAK) family; two members, IRAK4 and IRAK1, are sequentially phosphorylated, causing them to dissociate from the receptor complex, and then associate with TRAF6.
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
c85 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 15950447
The association of TLRs and MyD88 recruits members of the IL-1 receptor-associated kinase (IRAK) family; two members, IRAK4 and IRAK1, are sequentially phosphorylated, causing them to dissociate from the receptor complex, and then associate with TRAF6.
c86 cso30:c:InputProcess connector
c87 cso30:c:InputProcess connector
c88 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 15950447
TRAF6 forms a complex with ubiquitin-conjugating enzymes to activate the kinase TAK1, which in turn activates transcription factors nuclear factor (NF)-kappaB and activator protein-1 through the canonical IkappaB kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
c89 cso30:c:InputProcess connector
c90 cso30:c:InputProcess connector
c91 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 15950447
TRAF6 forms a complex with ubiquitin-conjugating enzymes to activate the kinase TAK1, which in turn activates transcription factors nuclear factor (NF)-kappaB and activator protein-1 through the canonical IkappaB kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
c93 cso30:c:InputAssociation connector
c96 cso30:c:InputProcess connector
c97 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 15950447
TRAF6 forms a complex with ubiquitin-conjugating enzymes to activate the kinase TAK1, which in turn activates transcription factors nuclear factor (NF)-kappaB and activator protein-1 through the canonical IkappaB kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
c92 cso30:c:InputAssociation connector
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 15950447
TRAF6 forms a complex with ubiquitin-conjugating enzymes to activate the kinase TAK1, which in turn activates transcription factors nuclear factor (NF)-kappaB and activator protein-1 through the canonical IkappaB kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
c98 cso30:c:InputProcess connector
c100 cso30:c:InputAssociation connector
c99 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 15950447
TRAF6 forms a complex with ubiquitin-conjugating enzymes to activate the kinase TAK1, which in turn activates transcription factors nuclear factor (NF)-kappaB and activator protein-1 through the canonical IkappaB kinase (IKK) complex and the mitogen-activated protein kinase pathway, respectively.
c101 cso30:c:InputProcess connector
c105 cso30:c:InputAssociation connector
c102 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 15950447, 15229469, 10435584
NF-kappaB activation by this ‘MyD88-dependent pathway’ results in the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, IL-6 and IL-1beta.
c103 cso30:c:InputProcess connector
c104 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 15950447, 15229469, 10435584
NF-kappaB activation by this ‘MyD88-dependent pathway’ results in the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, IL-6 and IL-1beta.
c109 cso30:c:InputAssociation connector
c106 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 15950447, 15229469, 10435584
NF-kappaB activation by this ‘MyD88-dependent pathway’ results in the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, IL-6 and IL-1beta.
c110 cso30:c:InputAssociation connector
c107 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 15950447, 15229469, 10435584
NF-kappaB activation by this ‘MyD88-dependent pathway’ results in the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, IL-6 and IL-1beta.
c111 cso30:c:InputAssociation connector
c108 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 15950447, 12447441, 12447442
Among these adapters, TIRAPMAL is required for the activation of the MyD88-dependent pathway downstream of TLR2 and TLR4.
c112 cso30:c:InputProcess connector
c113 cso30:c:InputProcess connector
c114 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 15950447, 12447441, 12447442
Among these adapters, TIRAPMAL is required for the activation of the MyD88-dependent pathway downstream of TLR2 and TLR4.
c115 cso30:c:InputProcess connector
c117 cso30:c:InputProcess connector
c116 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 15950447, 12447441, 12447442
Among these adapters, TIRAPMAL is required for the activation of the MyD88-dependent pathway downstream of TLR2 and TLR4.
c119 cso30:c:InputProcess connector
c118 cso30:c:InputProcess connector
c120 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 15950447, 12447441, 12447442
Among these adapters, TIRAPMAL is required for the activation of the MyD88-dependent pathway downstream of TLR2 and TLR4.
c121 cso30:c:InputProcess connector
c122 cso30:c:InputProcess connector
c123 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 15950447, 14556004
Additionally, TLR4 also requires another adaptor, TRAM, for IRF3 activation.
c124 cso30:c:InputProcess connector
c125 cso30:c:InputProcess connector
c126 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 15950447, 12855817, 12872135
It has been demonstrated that TRIF is responsible for TLR3- and TLR4-mediated IRF3 activation.
c130 cso30:c:InputProcess connector
c132 cso30:c:InputProcess connector
c131 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 15950447, 12855817, 12872135
It has been demonstrated that TRIF is responsible for TLR3- and TLR4-mediated IRF3 activation.
c127 cso30:c:InputProcess connector
c128 cso30:c:InputProcess connector
c129 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c133 cso30:c:InputProcess connector
c141 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c135 cso30:c:InputProcess connector
c143 cso30:c:InputAssociation connector
c136 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c137 cso30:c:InputProcess connector
c142 cso30:c:InputAssociation connector
c138 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c139 cso30:c:InputProcess connector
c144 cso30:c:InputAssociation connector
c140 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c149 cso30:c:InputProcess connector
c150 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 15950447, 12692549, 12702806
IRF3 activation occurs through the actions of the IKK-related kinases TRAF-family-member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and IKKi (also called IKKvar epsilon), which catalyze IRF3 phosphorylation and stimulate its nuclear translocation and DNA binding.
c145 cso30:c:InputProcess connector
c147 cso30:c:InputAssociation connector
c148 cso30:c:InputAssociation connector
c146 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 15950447, 11698465, 12855817
Stimulation of macrophages and DCs with LPS and dsRNA results in the activation of the transcription factor IFN regulatory factor 3 (IRF3) and subsequent induction of IFN-beta and IFN-inducible genes.
c153 cso30:c:InputAssociation connector
c151 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 15950447, 11698465, 12855817
Stimulation of macrophages and DCs with LPS and dsRNA results in the activation of the transcription factor IFN regulatory factor 3 (IRF3) and subsequent induction of IFN-beta and IFN-inducible genes.
c154 cso30:c:InputAssociation connector
c152 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 15950447, 14530355
TRAF6 is also reported to bind TRIF and cooperatively activate NF-kappaB.
c155 cso30:c:InputProcess connector
c156 cso30:c:InputProcess connector
c157 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 15950447, 14530355, 15064760
Furthermore, TRIF interacts with two different protein kinases, TBK1 and receptor-interacting protein-1 (RIP1).
c158 cso30:c:InputProcess connector
c159 cso30:c:InputProcess connector
c160 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 15950447, 14530355
TRAF6 is also reported to bind TRIF and cooperatively activate NF-kappaB.
c161 cso30:c:InputProcess connector
c162 cso30:c:InputProcess connector
c163 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 15950447, 11698465
However, cells doubly deficient in TRAF6 and MyD88 still partially activated NF-kappaB in response to LPS, suggesting that TRIF activates NF-kappaB through both TRAF6-dependent and -independent pathways in TLR4 signaling.
c164 cso30:c:InputProcess connector
c169 cso30:c:InputAssociation connector
c165 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 15950447
Thus, TRIF is likely to use TBK1 and RIP1 for IRF3- and NF-kappaB activation, respectively, in TLR3 signaling.
PMID: 15950447
In cells lacking RIP1, TLR3-mediated NF-kappaB activation and the subsequent induction of Icam-1 was severely impaired, whereas IFNbeta induction was intact.
c166 cso30:c:InputProcess connector
c168 cso30:c:InputAssociation connector
c167 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 15950447, 11698465
However, cells doubly deficient in TRAF6 and MyD88 still partially activated NF-kappaB in response to LPS, suggesting that TRIF activates NF-kappaB through both TRAF6-dependent and -independent pathways in TLR4 signaling.
c170 cso30:c:InputProcess connector
c172 cso30:c:InputAssociation connector
c171 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 15950447
In cells lacking RIP1, TLR3-mediated NF-kappaB activation and the subsequent induction of Icam-1 was severely impaired, whereas IFNbeta induction was intact.
c173 cso30:c:InputAssociation connector
c174 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 15950447, 12626561
It appears that IFN-alpha induction by TLR7 and TLR9 depends entirely on MyD88.
c176 cso30:c:InputProcess connector
c179 cso30:c:InputProcess connector
c180 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 15950447, 12626561
It appears that IFN-alpha induction by TLR7 and TLR9 depends entirely on MyD88.
c175 cso30:c:InputProcess connector
c177 cso30:c:InputProcess connector
c178 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 15950447, 15361868, 15492225
IRF7 forms a signaling complex with MyD88 and TRAF6 in the cytoplasm.
c185 cso30:c:InputProcess connector
c187 cso30:c:InputProcess connector
c186 cso30:c:OutputProcess connector
c188 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 15950447, 15361868, 15492225
IRF7 forms a signaling complex with MyD88 and TRAF6 in the cytoplasm.
c182 cso30:c:InputProcess connector
c183 cso30:c:InputProcess connector
c184 cso30:c:OutputProcess connector
p66_propro_p66
PMID: 15950447, 15361868, 15492225
IRF7 forms a signaling complex with MyD88 and TRAF6 in the cytoplasm.
c181 cso30:c:InputProcess connector
c192 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 15950447, 15361868, 15492225
IRF7 forms a signaling complex with MyD88 and TRAF6 in the cytoplasm.
c189 cso30:c:InputProcess connector
c190 cso30:c:InputProcess connector
c191 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 15950447
Similar to IRF3, phosphorylation is required for the activation of IRF7.
PMID: 15950447, 15767370
In this regard, IRAK1 has been demonstrated to serve as an IRF7 kinase, and in IRAK1-deficient mice, TLR7- and TLR9-induced IFN-alpha production was completely abolished, although inflammatory cytokines were produced.
c194 cso30:c:InputProcess connector
c195 cso30:c:OutputProcess connector
c198 cso30:c:OutputProcess connector
p69_propro_p69
PMID: 15950447
Similar to IRF3, phosphorylation is required for the activation of IRF7.
PMID: 15950447, 15767370
In this regard, IRAK1 has been demonstrated to serve as an IRF7 kinase, and in IRAK1-deficient mice, TLR7- and TLR9-induced IFN-alpha production was completely abolished, although inflammatory cytokines were produced.
c193 cso30:c:InputProcess connector
c196 cso30:c:OutputProcess connector
c197 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 15950447, 15361868, 15492225
After stimulation, IRF7 translocates into the nucleus to induce IFN-alpha.
c199 cso30:c:InputProcess connector
c200 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 15950447, 15361868, 15492225
After stimulation, IRF7 translocates into the nucleus to induce IFN-alpha.
c202 cso30:c:InputAssociation connector
c201 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 15950447
Accordingly, pDCs respond to CpG DNA, by rapidly secreting large amounts of IFN-alpha. Synthesized ssRNA can also induce IFN-alpha via TLR7.
c204 cso30:c:InputAssociation connector
c203 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 15950447, 15665823, 15695821
More recently, IRF5 has been shown to be involved in a MyD88TRAF6 complex.
c205 cso30:c:InputProcess connector
c206 cso30:c:InputProcess connector
c207 cso30:c:OutputProcess connector
p74_propro_p74
c208 cso30:c:InputProcess connector
c209 cso30:c:OutputProcess connector
c210 cso30:c:OutputProcess connector
p75_propro_p75
PMID: 15950447, 15665823
Upon TLR ligand stimulation, IRF5 was shown to translocate to the nucleus from the cytoplasm and bind the potential IFN-stimulated response element (ISRE) motifs present in the promoter region of proinflammatory cytokine genes.
c211 cso30:c:InputProcess connector
c212 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 15950447, 15665823
Upon TLR ligand stimulation, IRF5 was shown to translocate to the nucleus from the cytoplasm and bind the potential IFN-stimulated response element (ISRE) motifs present in the promoter region of proinflammatory cytokine genes.
c213 cso30:c:InputProcess connector
c215 cso30:c:InputProcess connector
c214 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 15950447
These observations indicate that IRF5 is a general signal transducer that mediates MyD88-dependent gene induction of proinflammatory cytokines, in contrast to IRF7, which requires MyD88-dependent IFN-alpha induction.
c217 cso30:c:InputAssociation connector
c216 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 15950447, 15153500
In these cells, TLR9-stimulated NF-kappaB activation was unexpectedly impaired, suggesting that IRF8 mediates NF-kappaB activation in TLR9 signaling.
c218 cso30:c:InputProcess connector
c220 cso30:c:InputAssociation connector
c219 cso30:c:OutputProcess connector
p79_propro_p79
PMID: 15950447, 15153500
In these cells, TLR9-stimulated NF-kappaB activation was unexpectedly impaired, suggesting that IRF8 mediates NF-kappaB activation in TLR9 signaling.
c221 cso30:c:InputProcess connector
c223 cso30:c:InputAssociation connector
c222 cso30:c:OutputProcess connector
p80_propro_p80
PMID: 15950447, 14978071, 15067049
For example, various TLR2 ligands induce abundant IL-10 and favor Th2-biased immune responses both in human and mice, whereas ligands for TLR4, TLR5 and TLR9 induce Th1-associated cytokines, such as IL-12p70.
PMID: 15950447
It was demonstrated that TLR2 ligands induce a higher phosphorylation of ERK and stabilization of the transcription factor c-Fos in DCs, which results in induction of IL-10 and suppression of IL-12p70.
c234 cso30:c:InputAssociation connector
c225 cso30:c:OutputProcess connector
p81_propro_p81
PMID: 15950447, 14978071, 15067049
For example, various TLR2 ligands induce abundant IL-10 and favor Th2-biased immune responses both in human and mice, whereas ligands for TLR4, TLR5 and TLR9 induce Th1-associated cytokines, such as IL-12p70.
PMID: 15950447
It was demonstrated that TLR2 ligands induce a higher phosphorylation of ERK and stabilization of the transcription factor c-Fos in DCs, which results in induction of IL-10 and suppression of IL-12p70.
c226 cso30:c:InputAssociation connector
c237 cso30:c:InputInhibitor connector
c229 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 15950447, 14978071, 15067049
For example, various TLR2 ligands induce abundant IL-10 and favor Th2-biased immune responses both in human and mice, whereas ligands for TLR4, TLR5 and TLR9 induce Th1-associated cytokines, such as IL-12p70.
PMID: 15950447
It was demonstrated that TLR2 ligands induce a higher phosphorylation of ERK and stabilization of the transcription factor c-Fos in DCs, which results in induction of IL-10 and suppression of IL-12p70.
c228 cso30:c:InputAssociation connector
c236 cso30:c:InputInhibitor connector
c230 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 15950447, 14978071, 15067049
For example, various TLR2 ligands induce abundant IL-10 and favor Th2-biased immune responses both in human and mice, whereas ligands for TLR4, TLR5 and TLR9 induce Th1-associated cytokines, such as IL-12p70.
PMID: 15950447
It was demonstrated that TLR2 ligands induce a higher phosphorylation of ERK and stabilization of the transcription factor c-Fos in DCs, which results in induction of IL-10 and suppression of IL-12p70.
c227 cso30:c:InputAssociation connector
c235 cso30:c:InputInhibitor connector
c231 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 15950447
It was demonstrated that TLR2 ligands induce a higher phosphorylation of ERK and stabilization of the transcription factor c-Fos in DCs, which results in induction of IL-10 and suppression of IL-12p70.
c232 cso30:c:InputAssociation connector
c224 cso30:c:InputProcess connector
c233 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 15950447
For example, intracellular introduction of dsRNA stimulates DCs lacking TLR3 to secrete type I IFN.
c238 cso30:c:InputAssociation connector
c240 cso30:c:InputAssociation connector
c239 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 15950447, 12855817, 15210742
TRIF but does require TBK1 and IRF3.
c241 cso30:c:InputAssociation connector
c242 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 15950447, 15208624
Retinoic acid-inducible gene I has recently been identified as an intracellular sensor for dsRNA, and is composed of the RNA helicase domain, which binds dsRNA, and the caspase recruitment domain (CARD), which culminates in IRF3 activation.
c243 cso30:c:InputProcess connector
c244 cso30:c:InputProcess connector
c245 cso30:c:OutputProcess connector
p88_propro_p88
PMID: 15950447, 15208624
Retinoic acid-inducible gene I has recently been identified as an intracellular sensor for dsRNA, and is composed of the RNA helicase domain, which binds dsRNA, and the caspase recruitment domain (CARD), which culminates in IRF3 activation.
PMID: 15950447, 15549108
Fas-associated death domain (FADD) and RIP1 have been demonstrated to be involved in this pathway.
c246 cso30:c:InputProcess connector
c248 cso30:c:InputAssociation connector
c249 cso30:c:InputAssociation connector
c250 cso30:c:InputAssociation connector
c247 cso30:c:OutputProcess connector
p89_propro_p89
PMID: 15950447, 15476921
NOD1 and NOD2 recognize naturally occurring degradation products and minimal motifs of bacterial peptidoglycan.
c251 cso30:c:InputProcess connector
c256 cso30:c:InputProcess connector
c252 cso30:c:OutputProcess connector
p90_propro_p90
PMID: 15950447, 15476921
NOD1 and NOD2 recognize naturally occurring degradation products and minimal motifs of bacterial peptidoglycan.
c253 cso30:c:InputProcess connector
c255 cso30:c:InputProcess connector
c254 cso30:c:OutputProcess connector
p91_propro_p91
PMID: 15950447, 15476921
NOD1 and NOD2 recognize naturally occurring degradation products and minimal motifs of bacterial peptidoglycan.
c257 cso30:c:InputProcess connector
c259 cso30:c:InputProcess connector
c261 cso30:c:OutputProcess connector
p92_propro_p92
PMID: 15950447, 15476921
NOD1 and NOD2 recognize naturally occurring degradation products and minimal motifs of bacterial peptidoglycan.
c258 cso30:c:InputProcess connector
c260 cso30:c:InputProcess connector
c262 cso30:c:OutputProcess connector
TLR4_enti_MO000019394
TLR4
LPS_enti_MO000016882
LPS
dsRNA_enti_MO000022224
dsRNA
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
TLR3_enti_MO000019398
TLR3
LPS: TLR4_enti_e5
LPS: TLR4
TLRs_enti_MO000019395
TLRs
TLR2_enti_MO000019397
TLR2
TLR5_enti_MO000019399
TLR5
TLR8_enti_MO000042007
TLR8
TLR9_enti_MO000042012
TLR9
TLR7_enti_MO000042126
TLR7
TLR2: TLR6_enti_e6
TLR2: TLR6
TLR2: TLR1_enti_e11
TLR2: TLR1
tri-acyi lipopeptide_enti_e12
tri-acyi lipopeptide
Di-acyl lipopeptide_enti_e13
Di-acyl lipopeptide
Di-acyl lipopeptide: TLR2: TLR6_enti_e14
Di-acyl lipopeptide: TLR2: TLR6
tri-acyi lipopeptide: TLR2: TLR1_enti_e15
tri-acyi lipopeptide: TLR2: TLR1
TRIF_enti_MO000041125
TRIF
MAL_enti_MO000068831
MAL
MyD88_enti_MO000016573
MyD88
PAMPs_enti_e16
PAMPs
PAMP: TLR_enti_e17
PAMP: TLR
IRAK-1_enti_MO000000213
IRAK-1
IRAK-4_enti_MO000039077
IRAK-4
TRAF6_enti_MO000000212
TRAF6
flagellin: TLR5_enti_e18
flagellin: TLR5
TAK1_enti_MO000016574
TAK1
flagellin_enti_MO000022185
flagellin
NF-kappaB_enti_MO000000058
NF-kappaB
IKK-alpha:IKK-beta:IKK-gamma_enti_MO000016661
IKK-alpha:IKK-beta:IKK-gamma
AP-1_enti_MO000000276
AP-1
TLR11_enti_MO000042130
TLR11
uropathogenic bacterial ligand: TLR11_enti_e19
uropathogenic bacterial ligand: TLR11
uropathogenic bacterial ligand_enti_e20
uropathogenic bacterial ligand
CpG DNA_enti_e21
CpG DNA
CpG DNA: TLR9_enti_e22
CpG DNA: TLR9
homozoin: TLR9_enti_e23
homozoin: TLR9
homozoin_enti_e24
homozoin
viral ssRNA_enti_e25
viral ssRNA
viral ssRNA: TLR8_enti_e26
viral ssRNA: TLR8
viral ssRNA: TLR7_enti_e27
viral ssRNA: TLR7
PGN: TLR2_enti_e28
PGN: TLR2
PGN_enti_MO000042032
PGN
lipopeptides_enti_e29
lipopeptides
lipopeptides: TLR2_enti_e30
lipopeptides: TLR2
Lp_enti_MO000017793
Lp
Lp: TLR2_enti_e31
Lp: TLR2
dectin-1_enti_e32
dectin-1
zymosan_enti_e33
zymosan
zymosan: TLR2: dectin-1_enti_e34
zymosan: TLR2: dectin-1
TLR ligands_enti_e35
TLR ligands
TLR2 ligands: CD36_enti_e36
TLR2 ligands: CD36
CD36_enti_e37
CD36
target genes_enti_e38
target genes
resiquimod_enti_e39
resiquimod
resiquimod: TLR8{h}_enti_e40
resiquimod: TLR8{h}
TLR8(h)_enti_MO000042006
TLR8(h)
resiquimod: TLR7_enti_e41
resiquimod: TLR7
imiquimod_enti_e42
imiquimod
imiquimod: TLR8{h}_enti_e43
imiquimod: TLR8{h}
imiquimod: TLR7_enti_e44
imiquimod: TLR7
loxoribine_enti_e45
loxoribine
loxoribine: TLR8{h}_enti_e47
loxoribine: TLR8{h}
loxoribine: TLR8{h}_enti_e46
loxoribine: TLR8{h}
West Nile Viru sligand: TLR3_enti_e48
West Nile Viru sligand: TLR3
West Nile Viru sligand_enti_e49
West Nile Viru sligand
PAMPs: TLR: MyD88_enti_e63
PAMPs: TLR: MyD88
PAMPs: TLR: MyD88 : IRAK-1: IRAK-4_enti_e64
PAMPs: TLR: MyD88 : IRAK-1: IRAK-4
PAMPs: TLR: MyD88 : IRAK-1: IRAK-4{p}_enti_e65
PAMPs: TLR: MyD88 : IRAK-1: IRAK-4{p}
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}_enti_e67
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}
IRAK-1{p}: IRAK-4{p}_enti_e68
IRAK-1{p}: IRAK-4{p}
IRAK-1{p}: IRAK-4{p}: TRAF6_enti_e69
IRAK-1{p}: IRAK-4{p}: TRAF6
IRAK-1{p}: IRAK-4{p}: TRAF6: TAK1_enti_e70
IRAK-1{p}: IRAK-4{p}: TRAF6: TAK1
MAPKs_enti_MO000000077
MAPKs
MAPKs{activated}_enti_e71
MAPKs{activated}
IKK-alpha:IKK-beta:IKK-gamma{activated}_enti_e72
IKK-alpha:IKK-beta:IKK-gamma{activated}
NF-kappaB{activated}_enti_e73
NF-kappaB{activated}
AP-1{activated}_enti_e74
AP-1{activated}
NF-kappaB{nucleus}_enti_e75
NF-kappaB{nucleus}
TNF-alpha_enti_G010329
TNF-alpha
IL-6_enti_G010262
IL-6
IL-1beta_enti_G010389
IL-1beta
LPS: TLR4: MAL_enti_e66
LPS: TLR4: MAL
LPS: TLR4: MAL: MyD88_enti_e76
LPS: TLR4: MAL: MyD88
Lp: TLR2: MAL_enti_e77
Lp: TLR2: MAL
Lp: TLR2: MAL: MyD88_enti_e78
Lp: TLR2: MAL: MyD88
TRAM_enti_MO000041132
TRAM
LPS: TLR4: TRAM_enti_e79
LPS: TLR4: TRAM
LPS: TLR4: TRAM: TRIF_enti_e80
LPS: TLR4: TRAM: TRIF
dsRNA: TLR3: TRIF_enti_e81
dsRNA: TLR3: TRIF
TBK1_enti_MO000019331
TBK1
TBK1{activated}_enti_e82
TBK1{activated}
IKK-i_enti_MO000016608
IKK-i
IKK-i{activated}_enti_e83
IKK-i{activated}
IRF-3_enti_MO000007694
IRF-3
IRF-3{p}_enti_MO000041456
IRF-3{p}
IRF-3{p}{nucleus}_enti_e84
IRF-3{p}{nucleus}
IFN-beta_enti_G010228
IFN-beta
IFN inducible gene_enti_e85
IFN inducible gene
RIP1_enti_MO000000065
RIP1
LPS: TLR4: TRAM: TRIF_enti_e86
LPS: TLR4: TRAM: TRIF
dsRNA: TLR3: TRIF: RIP1_enti_e87
dsRNA: TLR3: TRIF: RIP1
dsRNA: TLR3: TRIF: RIP1: TRAF6_enti_e88
dsRNA: TLR3: TRIF: RIP1: TRAF6
ICAM-1_enti_G010431
ICAM-1
viral ssRNA: TLR7: MyD88_enti_e89
viral ssRNA: TLR7: MyD88
CpG DNA: TLR9: MyD88_enti_e90
CpG DNA: TLR9: MyD88
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}_enti_e91
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6_enti_e92
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}_enti_e93
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6_enti_e94
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6
IRF-7_enti_MO000007702
IRF-7
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6: IRF-7_enti_e95
viral ssRNA: TLR7: MyD88: IRAK-1{p}: IRAK-4{p}: TRAF6: IRF-7
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}: IRF-7_enti_e96
CpG DNA: TLR9: MyD88: IRAK-1{p}: IRAK-4{p}: IRF-7
IRF-7{p}_enti_MO000041457
IRF-7{p}
IFN-alpha_enti_G016992
IFN-alpha
IRF-7{p}{nucleus}_enti_e97
IRF-7{p}{nucleus}
IFNalpha_enti_MO000016659
IFNalpha
IRF-5_enti_MO000007700
IRF-5
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}: TRAF6_enti_e98
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}: TRAF6
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}: TRAF6: IRF-5_enti_e99
PAMPs: TLR: MyD88 : IRAK-1{p}: IRAK-4{p}: TRAF6: IRF-5
IRF-5{activated}_enti_e100
IRF-5{activated}
IRF-5{nucleus}_enti_e101
IRF-5{nucleus}
IRF-5: proinflammatory cytokines_enti_e102
IRF-5: proinflammatory cytokines
proinflammatory cytokines_enti_e103
proinflammatory cytokines
proinflammatory cytokines_enti_e104
proinflammatory cytokines
IRF-8_enti_MO000007185
IRF-8
IRF-8{activated}_enti_e105
IRF-8{activated}
IL10_enti_G011345
IL10
IL-12p70_enti_e106
IL-12p70
ERK_enti_MO000000011
ERK
ERK{p}_enti_MO000038306
ERK{p}
IFN Type I_enti_MO000016658
IFN Type I
IFN Type I_enti_e107
IFN Type I
RIG-1_enti_e108
RIG-1
dsRNA: RIG-1_enti_e109
dsRNA: RIG-1
FADD_enti_MO000016899
FADD
Nod1_enti_MO000020434
Nod1
PGN: Nod1_enti_e110
PGN: Nod1
PGN: NOD2_enti_e111
PGN: NOD2
Nod2_enti_MO000020461
Nod2
protein remnants_enti_MO000019479
protein remnants
protein remnants: NOD1_enti_e112
protein remnants: NOD1
protein remnants: NOD2_enti_e113
protein remnants: NOD2