_enti_e7
_enti_e8
_enti_e1
_enti_e9
_enti_e10
_enti_e3
_enti_e2
_enti_e4
_enti_e55
_enti_e75
_enti_e59
_enti_e53
_enti_e74
_enti_e76
_enti_e51
_enti_e52
_enti_e54
_enti_e50
_enti_e56
_enti_e58
_enti_e61
_enti_e57
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g3
p1_propro_p1
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 16343886, 15795223
The hypothesised model here involves the assembly of a TIRTIR platform by the dimerization of two TLRs.
c18 cso30:c:InputProcess connector
c34 cso30:c:InputProcess connector
c35 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 16343886
he most characterised are the recognition of double stranded RNA (dsRNA) by TLR3 and recognition of CpG motifs in DNA by TLR9.
c36 cso30:c:InputProcess connector
c37 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c7 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 16343886
It now appears, however, that CD14 can influence signalling by TLR4, and is required for activation of the TrifTram pathway by TLR4 because when CD14 is absent LPS can only engage with the MyD88 pathway.
PMID: 16343886
This is also the case with TLR4, but only when so-called ‘smooth’ LPS, which has longer O-polysaccharide chains compared to ‘rough’ LPS, is used as a ligand.
c10 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c11 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 16343886
It now appears, however, that CD14 can influence signalling by TLR4, and is required for activation of the TrifTram pathway by TLR4 because when CD14 is absent LPS can only engage with the MyD88 pathway.
PMID: 16343886
This is also the case with TLR4, but only when so-called ‘smooth’ LPS, which has longer O-polysaccharide chains compared to ‘rough’ LPS, is used as a ligand.
c12 cso30:c:InputProcess connector
c13 cso30:c:InputProcess connector
c14 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 16343886, 15690042
A role for other co-receptors is also emerging, with CD36 shown to be an essential co-receptor for TLR2.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c20 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 16343886, 15690042
A role for other co-receptors is also emerging, with CD36 shown to be an essential co-receptor for TLR2.
c21 cso30:c:InputProcess connector
c15 cso30:c:InputProcess connector
c19 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c24 cso30:c:InputProcess connector
c25 cso30:c:InputProcess connector
c26 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c27 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 16343886
Lipid-based structures are recognized by TLR2 (in combination with TLR1 or TLR6 as heterodimers) and TLR4 (as a homodimer): the most studied examples of lipid-based recognition are bacterial or mycobacterial lipopeptides, or glycerophosphatidylinositol anchors from parasites, both of which are recognized by TLR2, and bacterial lipopolysaccharide (LPS), which is recognized by TLR4.
c31 cso30:c:InputProcess connector
c32 cso30:c:InputProcess connector
c33 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 16343886, 15860593
Finally, TLR5 and TLR11 recognize proteins from pathogens (flagellin in the case of TLR5 and profilin in the case of TLR11 [only in the mouse]).
c38 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c41 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 16343886, 15860593
Finally, TLR5 and TLR11 recognize proteins from pathogens (flagellin in the case of TLR5 and profilin in the case of TLR11 [only in the mouse]).
c42 cso30:c:InputProcess connector
c43 cso30:c:InputProcess connector
c44 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 16343886
he most characterised are the recognition of double stranded RNA (dsRNA) by TLR3 and recognition of CpG motifs in DNA by TLR9.
c45 cso30:c:InputProcess connector
c46 cso30:c:InputProcess connector
c47 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 16343886, 15795223
The hypothesised model here involves the assembly of a TIRTIR platform by the dimerization of two TLRs.
c48 cso30:c:InputProcess connector
c49 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 16343886
This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).
PMID: 16343886, 15004556
An early demonstration of this was the observation that ST2, which is another member of the IL-1R subgroup of TIR proteins, inhibits TLR signalling in macrophages by sequestering MyD88 and Mal from signalling pathways.
c50 cso30:c:InputProcess connector
c92 cso30:c:InputProcess connector
c141 cso30:c:InputInhibitor connector
c52 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 16343886
This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).
PMID: 16343886
MyD88s lacks a region important for IRAK-4 recruitment and so IRAK-4 is not engaged, hence limiting NF-kappaB activation.
c53 cso30:c:InputProcess connector
c54 cso30:c:InputProcess connector
c91 cso30:c:InputProcess connector
c140 cso30:c:InputInhibitor connector
c56 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 16343886
This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).
c60 cso30:c:InputProcess connector
c58 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 16343886
This platform then recruits MyD88, leading in turn to the recruitment of IRAK-4 (whose death domain interacts with the death domain of MyD88). IRAK-4 becomes activated and phosphorylates IRAK-1 (which might already be in the complex, as it also has a death domain).
c57 cso30:c:InputProcess connector
c59 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 16343886
Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.
c61 cso30:c:InputProcess connector
c62 cso30:c:OutputProcess connector
c63 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 16343886
Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.
c64 cso30:c:InputProcess connector
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 16343886
Phosphorylated IRAK-1 is active, and then somehow activates Traf-6.
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c69 cso30:c:InputProcess connector
c70 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c71 cso30:c:InputProcess connector
c72 cso30:c:InputProcess connector
c73 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c74 cso30:c:InputProcess connector
c75 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c76 cso30:c:InputAssociation connector
c77 cso30:c:InputProcess connector
c78 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c79 cso30:c:InputAssociation connector
c81 cso30:c:InputProcess connector
c82 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c80 cso30:c:InputAssociation connector
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 16343886
A series of ubiquitinylation reactions then occur on Traf-6 itself and on the protein kinase TAK-1, which is a candidate kinase for the activation of the inhibitor of NF-kappaB kinase (IKK) complex, leading to NF-kappaB activation, and activation of upstream kinases for p38 and JNK.
c85 cso30:c:InputProcess connector
c87 cso30:c:InputAssociation connector
c86 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 16343886, 11544529, 11526399
The discovery of the second TIR domain-containing adaptor, MyD88 adaptor-like (Mal), also known as TIRAP, indicated that there might be specificity in the signalling pathways, particularly when Mal was shown to have a role in TLR4, but not IL-1, signalling to NF-kappaB.
PMID: 16343886, 15004556
An early demonstration of this was the observation that ST2, which is another member of the IL-1R subgroup of TIR proteins, inhibits TLR signalling in macrophages by sequestering MyD88 and Mal from signalling pathways.
c88 cso30:c:InputProcess connector
c89 cso30:c:InputProcess connector
c136 cso30:c:InputProcess connector
c142 cso30:c:InputInhibitor connector
c90 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 16343886, 15849357
MyD88 homodimerization has been shown to involve another region of the TIR domain called Box 3.
c51 cso30:c:InputProcess connector
c55 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 16343886, 12471095, 12692549
A third adaptor was then described, termed TIR-related adaptor protein inducing interferon (Trif), which is recruited by both TLR4 and TLR3, and is responsible for activation of IRF3 [10, 11 and 12], acting via an IKK-like kinase termed TBK-1.
PMID: 16343886, 14517278, 14519765, 14556004
The fourth adaptor to be described was named Trif-related adaptor molecule (Tram), and interestingly acts only in TLR4 signalling, where it interacts with Trif.
c93 cso30:c:InputProcess connector
c94 cso30:c:InputProcess connector
c97 cso30:c:InputProcess connector
c99 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 16343886, 12471095, 12692549
A third adaptor was then described, termed TIR-related adaptor protein inducing interferon (Trif), which is recruited by both TLR4 and TLR3, and is responsible for activation of IRF3 [10, 11 and 12], acting via an IKK-like kinase termed TBK-1.
c95 cso30:c:InputProcess connector
c98 cso30:c:InputProcess connector
c100 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
c101 cso30:c:InputProcess connector
c102 cso30:c:InputProcess connector
c103 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
c104 cso30:c:InputProcess connector
c105 cso30:c:InputProcess connector
c106 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
PMID: 16343886
TLR3 activates IRF3 homodimers which then bind the interferon sensitive response element (ISRE) on target genes, such as IFN-beta.
c107 cso30:c:InputAssociation connector
c109 cso30:c:InputProcess connector
c110 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
PMID: 16343886, 1455726
For TLR4, a complex of p65 and IRF3 is activated.
c108 cso30:c:InputAssociation connector
c111 cso30:c:InputProcess connector
c112 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
PMID: 16343886
This limits the induction of IFN-beta by TLR3 during infection and might contribute to the persistence of the virus.
c113 cso30:c:InputAssociation connector
c114 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 16343886, 15849357
A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.
c96 cso30:c:InputProcess connector
c116 cso30:c:InputProcess connector
c115 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 16343886, 15849357
A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.
c117 cso30:c:InputProcess connector
c119 cso30:c:InputProcess connector
c118 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 16343886, 15849357
A recent study has, however, identified three other amino acids in the BB loop of MyD88 (Asp195, Arg196 and Asp197) as important for interaction with the IL-1 receptor accessory protein (IL-1AcP, which also has a TIR domain and is required for IL-1 signalling in complex with IL-1RI.
c120 cso30:c:InputProcess connector
c121 cso30:c:InputProcess connector
c122 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 16343886
It appears that activation of Trif by LPS leads to the rapid production of TNF, which is dependent on IRF3.
c123 cso30:c:InputAssociation connector
c125 cso30:c:InputAssociation connector
c124 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 16343886
Perhaps TNF induction requires an interplay between NF-kappaB, activated by MyD88, and IRF3, activated by Trif, whereas IFN-beta only requires IRF3.
c127 cso30:c:InputAssociation connector
c126 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 16343886
TLR9, similar to IL-1, apparently only requires MyD88 for signalling, and yet, unlike IL-1, is a strong inducer of IFN-alpha, but only in plasmacytoid dendritic cells.
c128 cso30:c:InputProcess connector
c129 cso30:c:InputProcess connector
c130 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 16343886
TLR9, similar to IL-1, apparently only requires MyD88 for signalling, and yet, unlike IL-1, is a strong inducer of IFN-alpha, but only in plasmacytoid dendritic cells.
c135 cso30:c:InputAssociation connector
c132 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 16343886, 15815647, 15800576, 15767370
Honda and colleagues now provide an explanation for this: IFN-alpha production requires the transcription factor IRF7, and this protein has been shown to associate with MyD88.In plasmacytoid dendritic cells, the IFN-alpha-inducing TLR9 ligand CpG-A is retained for long periods in endosomal vesicles together with the MyD88IRF7 complex.
c131 cso30:c:InputProcess connector
c133 cso30:c:InputProcess connector
c134 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 16343886
MyD88s lacks a region important for IRAK-4 recruitment and so IRAK-4 is not engaged, hence limiting NF-kappaB activation.
c137 cso30:c:InputProcess connector
c138 cso30:c:InputProcess connector
c139 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 16343886, 15623538
TGF-beta blocks TLR signalling by causing the ubiquitinylation and proteasomal degradation of MyD88 [36]. This may be a key aspect of the anti-inflammatory effects of TGF-beta.
c143 cso30:c:InputProcess connector
c145 cso30:c:InputAssociation connector
c144 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 16343886, 15623538
TGF-beta blocks TLR signalling by causing the ubiquitinylation and proteasomal degradation of MyD88 [36]. This may be a key aspect of the anti-inflammatory effects of TGF-beta.
c146 cso30:c:InputProcess connector
c147 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 16343886, 15710891
Also of interest is the observation that the hepatitis C virus protein NS3/4A can cleave and inactivate Trif.
c148 cso30:c:InputProcess connector
c150 cso30:c:InputAssociation connector
c149 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 16343886, 15800576, 15767370, 15361868
IRF7 is a key transcription factor for induction of type I interferons, and its activation occurs by both MyD88-dependent pathways (activated by TLR9) and Trif pathways (activated via TBK-1).
c152 cso30:c:InputProcess connector
c156 cso30:c:InputAssociation connector
c153 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 16343886, 15800576, 15767370, 15361868
IRF7 is a key transcription factor for induction of type I interferons, and its activation occurs by both MyD88-dependent pathways (activated by TLR9) and Trif pathways (activated via TBK-1).
c154 cso30:c:InputProcess connector
c157 cso30:c:InputAssociation connector
c155 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 16343886
IRF7 associates directly with both IRAK-4 and IRAK-1.
c158 cso30:c:InputProcess connector
c159 cso30:c:InputProcess connector
c161 cso30:c:InputProcess connector
c160 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 16343886
IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.
c162 cso30:c:InputProcess connector
c163 cso30:c:InputProcess connector
c164 cso30:c:InputProcess connector
c165 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 16343886
IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.
c169 cso30:c:InputAssociation connector
c166 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 16343886
IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.
c171 cso30:c:InputAssociation connector
c167 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 16343886
IRF5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12 and TNF, but not IFN-alpha, and is found in a trimeric complex with MyD88 and Traf6.
c170 cso30:c:InputAssociation connector
c168 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 16343886
The discovery of Trif provided the first molecular basis for why TLR3 and TLR4, but not TLR2, are able to induce IFN-beta both TLR3 and TLR4 can signal via Trif to the IKK family kinase TBK-1, which phosphorylates IRF3.
PMID: 16343886
This limits the induction of IFN-b
by TLR3 during infection and might contribute to the
persistence of the virus.
c172 cso30:c:InputAssociation connector
c151 cso30:c:InputInhibitor connector
c173 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 16343886
A notable example of a gene activated by this pathway is IL-6, which is regulated by IkappaB-zeta in a complex with p50.
c174 cso30:c:InputProcess connector
c175 cso30:c:InputProcess connector
c176 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 16343886, 15665823
Another IRF, IRF5, is found downstream of MyD88, and
so is activated by multiple TLRs
c177 cso30:c:InputProcess connector
c179 cso30:c:InputAssociation connector
c178 cso30:c:OutputProcess connector
TLR2_enti_MO000019397
TLR2
TLR4_enti_MO000019394
TLR4
TLRs_enti_MO000019395
TLRs
TLR1_enti_MO000019396
TLR1
TLR3_enti_MO000019398
TLR3
TLR5_enti_MO000019399
TLR5
TLR6_enti_MO000019422
TLR6
CD14_enti_MO000018132
CD14
TLR11_enti_MO000042130
TLR11
MyD88_enti_MO000016573
MyD88
TLR9_enti_MO000042012
TLR9
MAL_enti_MO000068831
MAL
TRIF_enti_MO000041125
TRIF
TRAM_enti_MO000041132
TRAM
Irak1_enti_e5
Irak1
IRAK-4_enti_MO000039077
IRAK-4
TRAF6_enti_MO000000212
TRAF6
LPS_enti_MO000016882
LPS
lipopeptides_enti_e6
lipopeptides
TLR2: TLR6_enti_e11
TLR2: TLR6
TLR2: TLR1_enti_e12
TLR2: TLR1
glycerophosphatidylinositol_enti_e13
glycerophosphatidylinositol
TLR4: TLR4_enti_e14
TLR4: TLR4
LPS: CD14_enti_e15
LPS: CD14
LPS: CD14: TLR4: TLR4_enti_e16
LPS: CD14: TLR4: TLR4
CD36_enti_e17
CD36
lipopeptides: CD36_enti_e18
lipopeptides: CD36
glycerophosphatidylinositol: CD36_enti_e19
glycerophosphatidylinositol: CD36
NF-kappaB_enti_MO000000058
NF-kappaB
glycerophosphatidylinositol: CD36: TLR2: TLR1_enti_e20
glycerophosphatidylinositol: CD36: TLR2: TLR1
lipopeptides: CD36: TLR2: TLR6_enti_e21
lipopeptides: CD36: TLR2: TLR6
glycerophosphatidylinositol: CD36: TLR2: TLR6_enti_e22
glycerophosphatidylinositol: CD36: TLR2: TLR6
lipopeptides: CD36: TLR2: TLR1_enti_e23
lipopeptides: CD36: TLR2: TLR1
TLR ligand_enti_e24
TLR ligand
TLR ligand: TLR_enti_e25
TLR ligand: TLR
dsRNA_enti_MO000022224
dsRNA
flagellin_enti_MO000022185
flagellin
dsRNA: TLR3_enti_e26
dsRNA: TLR3
flagellin: TLR5_enti_e27
flagellin: TLR5
flagellin: TLR11_enti_e28
flagellin: TLR11
CpG DNA_enti_e29
CpG DNA
CpG DNA: TLR9_enti_e30
CpG DNA: TLR9
TLR ligand: TLR: TLR_enti_e31
TLR ligand: TLR: TLR
TLR ligand: TLR: TLR: MyD88_enti_e32
TLR ligand: TLR: TLR: MyD88
TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1_enti_e33
TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1
TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1{p}_enti_e34
TLR ligand: TLR: TLR: MyD88: IRAK-4: IRAK1{p}
TLR ligand: TLR: TLR: MyD88: IRAK-4 (activated): IRAK1_enti_e35
TLR ligand: TLR: TLR: MyD88: IRAK-4 (activated): IRAK1
TLR ligand: TLR: TLR: MyD88: IRAK-4_enti_e36
TLR ligand: TLR: TLR: MyD88: IRAK-4
IRAK1 {p}_enti_e37
IRAK1 {p}
IRAK1 {p}: TRAF6_enti_e38
IRAK1 {p}: TRAF6
IRAK1 {p}: TRAF6 {activated}_enti_e39
IRAK1 {p}: TRAF6 {activated}
IRAK1 {p}: TRAF6 {ub}_enti_e40
IRAK1 {p}: TRAF6 {ub}
TAK1_enti_MO000016574
TAK1
IRAK1 {p}: TRAF6 {ub}: TAK1_enti_e41
IRAK1 {p}: TRAF6 {ub}: TAK1
IRAK1 {p}: TRAF6 {ub}: TAK1 {ub}_enti_e42
IRAK1 {p}: TRAF6 {ub}: TAK1 {ub}
IKK-alpha:IKK-beta:IKK-gamma_enti_e43
IKK-alpha:IKK-beta:IKK-gamma
IKK-alpha:IKK-beta:IKK-gamma {activated}_enti_e44
IKK-alpha:IKK-beta:IKK-gamma {activated}
p38_enti_MO000000022
p38
p38 {activated}_enti_e45
p38 {activated}
JNK_enti_MO000000023
JNK
JNK {activated}_enti_e46
JNK {activated}
NF-kappaB {activated}_enti_e47
NF-kappaB {activated}
LPS: CD14: TLR4: TLR4: MyD88: MAL_enti_e48
LPS: CD14: TLR4: TLR4: MyD88: MAL
TLR ligand: TLR: TLR: MyD88: MyD88_enti_e49
TLR ligand: TLR: TLR: MyD88: MyD88
LPS: CD14: TLR4: TLR4: TRIF: TRAM_enti_e63
LPS: CD14: TLR4: TLR4: TRIF: TRAM
dsRNA: TLR3: TRIF_enti_e64
dsRNA: TLR3: TRIF
LPS: CD14: TLR4: TLR4: TRIF: TRAM: TBK1_enti_e65
LPS: CD14: TLR4: TLR4: TRIF: TRAM: TBK1
TBK1_enti_MO000019331
TBK1
dsRNA: TLR3: TRIF: TBK1_enti_e66
dsRNA: TLR3: TRIF: TBK1
RelA p65: IRF-3 {p}_enti_e67
RelA p65: IRF-3 {p}
IFN-beta_enti_G010228
IFN-beta
IL-1AcP: MyD88_enti_e68
IL-1AcP: MyD88
IL-1RI_enti_MO000016595
IL-1RI
IL-1AcP_enti_e69
IL-1AcP
IL-1: IL-1RI_enti_e70
IL-1: IL-1RI
IL-1_enti_MO000000214
IL-1
IL-1: IL-1RI: IL-AcP: MyD88_enti_e71
IL-1: IL-1RI: IL-AcP: MyD88
TNF-alpha_enti_MO000000289
TNF-alpha
TNF-alpha_enti_G010329
TNF-alpha
CpG DNA: TLR9: MyD88_enti_e72
CpG DNA: TLR9: MyD88
IFN-alpha_enti_e73
IFN-alpha
IRF-7_enti_MO000007702
IRF-7
CpG DNA: TLR9: MyD88: IRF-7_enti_e77
CpG DNA: TLR9: MyD88: IRF-7
MyD88s_enti_e78
MyD88s
TLR ligand: TLR: TLR: MyD88s_enti_e79
TLR ligand: TLR: TLR: MyD88s
ST2_enti_MO000044786
ST2
MyD88 {ub}_enti_e81
MyD88 {ub}
TGFbeta_enti_MO000016808
TGFbeta
protein remnants_enti_MO000019479
protein remnants
NS3/4A_enti_e80
NS3/4A
TRIF {inactive}_enti_e82
TRIF {inactive}
IRF-7 {activated}_enti_e83
IRF-7 {activated}
iRAK-4: iRAK1: IRF-7_enti_e84
iRAK-4: iRAK1: IRF-7
IRF-5{active}_enti_MO000007700
IRF-5{active}
MyD88: TRAF6: IRF-5_enti_e85
MyD88: TRAF6: IRF-5
IL-6_enti_G010262
IL-6
IL-12 p40_enti_G010657
IL-12 p40
IRF-3: IRF-3_enti_e86
IRF-3: IRF-3
IRF-3: IRF-3 {p}_enti_e87
IRF-3: IRF-3 {p}
RelA p65: IRF-3_enti_e88
RelA p65: IRF-3
IkappaB-zeta_enti_e89
IkappaB-zeta
p50_enti_MO000000200
p50
IkappaB-zeta: p50_enti_e90
IkappaB-zeta: p50
IRF-5_enti_e91
IRF-5