Original Literature | Model OverView |
---|---|
Publication
Title
Adaptor usage and Toll-like receptor signaling specificity.
Affiliation
Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland.aidunne@tcd.ie
Abstract
It is now well established that Toll-like receptors (TLRs) act as primarysensors of microbial compounds. Details of the molecular mechanisms governingTLR responses are emerging steadily and our understanding of the signalingpathways activated these receptors has improved greatly over the last few years.Differences in adaptor usage, cellular localisation and signaling cascades havebeen elucidated. In this review we will summarize the current understanding ofTLR signaling and its regulation.
PMID
15876435
|
Entity
PI3K
--
MO000000030
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m48
10
infinite
0
TRANSPATH | MO000000030 |
--
NF-kappaB{active}
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m26
10
infinite
0
TRANSPATH | MO000000058 |
--
TRAF6
--
MO000000212
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m183
10
infinite
0
InterPro | IPR001841 |
TRANSPATH | MO000000212 |
--
IRF-7
--
MO000007702
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m980
10
infinite
0
TRANSPATH | MO000007702 |
--
IRAK-M
--
MO000016569
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1571
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016569 |
--
MyD88
--
MO000016573
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1572
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000016573 |
--
IKK-i
--
MO000016608
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1599
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016608 |
--
fibrinogen
--
MO000017426
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m2254
10
infinite
0
TRANSPATH | MO000017426 |
--
fibronectin
--
MO000017549
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m2341
10
infinite
0
InterPro | IPR006209 |
TRANSPATH | MO000017549 |
--
TBK1
--
MO000019331
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3902
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000019331 |
--
TLR4
--
MO000019394
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3961
10
infinite
0
InterPro | IPR000157 |
TRANSPATH | MO000019394 |
--
protein remnants
--
MO000019479
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m360980
10
infinite
0
TRANSPATH | MO000019479 |
--
dsRNA:TLR3
--
MO000041446
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m19314
10
infinite
0
TRANSPATH | MO000041446 |
--
IRF-7{p}
--
MO000041457
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m19325
10
infinite
0
TRANSPATH | MO000041457 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
--
e10
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m10
0
infinite
0
--
Hsp60:TLR4
--
e11
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m11
0
infinite
0
--
HSP70:TLR4
--
e12
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m12
0
infinite
0
--
fibronectin:TLR4
--
e13
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m13
0
infinite
0
--
(LPS:TLR4)2
--
e14
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m14
0
infinite
0
--
(LPS:TLR4)2:TIRAP
--
e15
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m15
0
infinite
0
--
(LPS:TLR4)2:TIRAP:MYD88
--
e16
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m16
0
infinite
0
--
(LPS:TLR4)2:TIRAP:MYD88:IRAK4
--
e17
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m17
0
infinite
0
--
IRAK1
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m18
0
infinite
0
--
(LPS:TLR4)2:TIRAP:MYD88:IRAK4:IRAK1
--
e19
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
(LPS:TLR4)2:TIRAP:MYD88:IRAK4:IRAK1{p}
--
e20
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m20
0
infinite
0
--
IRAK1{p}:TRAF6
--
e21
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m21
0
infinite
0
--
IRAK1{p}:TRAF6
--
e22
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m22
0
infinite
0
--
TAK1:TAB1:TAB2 {active}
--
e23
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m23
0
infinite
0
--
TAK1:TAB1:TAB2
--
e24
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m24
0
infinite
0
--
NF-kappaB
--
e26
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m27
10
infinite
0
TRANSPATH | MO000000058 |
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
(LPS:TLR4)2:TRAM
--
e31
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m34
0
infinite
0
--
(LPS:TLR4)2:TRAM:TRIF
--
e32
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m35
0
infinite
0
--
(LPS:TLR4)2:TRAM:TRIF:TRAF6
--
e33
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m36
0
infinite
0
--
(LPS:TLR4)2:TRAM:TRIF:TBK1:IKK-i
--
e34
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m37
0
infinite
0
--
(LPS:TLR4)2:TRAM:TRIF:RIP1
--
e35
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m39
0
infinite
0
--
TLR1:TLR2
--
e37
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m41
0
infinite
0
--
TLR2:TLR6
--
e38
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m42
0
infinite
0
--
triacyl lipopeptide
--
e39
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m43
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
triacyl lipopeptide:TLR1:TLR2
--
e40
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m44
0
infinite
0
--
diacyl lipopeptide
--
e41
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m45
0
infinite
0
--
diacyl lipopeptide:TLR2:TLR6
--
e42
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m46
0
infinite
0
--
diacyl lipopeptide:TLR2{p}:TLR6
--
e43
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m47
0
infinite
0
--
diacyl lipopeptide:TLR2{p}:TLR6:PI3K
--
e44
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m49
0
infinite
0
--
diacyl lipopeptide:TLR2{p}:TLR6:PI3K:Rac1
--
e45
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m63
0
infinite
0
--
(LPS:TLR4):TIRAP:MYD88:PI3K
--
e46
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m64
0
infinite
0
--
ssRNA:TLR7
--
e47
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m65
0
infinite
0
--
flagellin:TLR5
--
e48
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m66
0
infinite
0
--
--
e49
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeMembrane
--
--
--
csml-variable:Double
m67
0
infinite
0
--
LPS:TLR4
--
e5
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
csml-variable:Double
m5
0
infinite
0
--
--
e50
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m50
0
infinite
0
--
--
e51
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m51
0
infinite
0
--
--
e52
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m52
0
infinite
0
--
--
e53
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m53
0
infinite
0
--
--
e54
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m54
0
infinite
0
--
--
e55
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m55
0
infinite
0
--
--
e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m56
0
infinite
0
--
--
e57
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m57
0
infinite
0
--
--
e58
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m58
0
infinite
0
--
--
e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m59
0
infinite
0
--
fibrinogen:TLR4
--
e6
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m6
0
infinite
0
--
--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m60
0
infinite
0
--
--
e61
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m61
0
infinite
0
--
--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m62
0
infinite
0
--
--
e63
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Endosome
--
--
--
csml-variable:Double
m68
0
infinite
0
--
--
e64
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeLumen
--
--
--
csml-variable:Double
m69
0
infinite
0
--
CpG DNA:TLR9
--
e65
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m70
0
infinite
0
--
csml-variable:Double
m71
0
infinite
0
--
RNA
--
e67
cso30:c:Rna
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m72
0
infinite
0
--
IFN-alpha
--
e68
cso30:c:mRNA
cso30:i:CC_Cytosol
--
csml-variable:Double
m73
0
infinite
0
--
dsRNA:TLR3{p}:TRIF:PI3K
--
e69
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m74
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
dsRNA:TLR3:TRIF:RIP1
--
e70
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m75
0
infinite
0
--
dsRNA:TLR3:TRIF:TBK1:IKK-i:NAP1
--
e71
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m76
0
infinite
0
--
NAP1
--
e72
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m77
0
infinite
0
--
dsRNA:TLR3{p}
--
e73
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m78
0
infinite
0
--
CpG DNA:TLR9:IRF7:MYD88:TRAF6
--
e74
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m79
0
infinite
0
--
ssRNA:TLR7:MYD88:TRAF6:IRF5
--
e75
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m80
0
infinite
0
--
MYD88s
--
e76
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m81
0
infinite
0
--
(LPS:TLR4)2:TIRAP:MYD88:IRAK4
--
e77
cso30:c:Complex
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m82
0
infinite
0
--
IRAK1{p}
--
e78
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m83
0
infinite
0
--
ubiquitin
--
e79
cso30:c:SmallMolecule
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m84
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
Triad3A
--
e80
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m85
0
infinite
0
--
Triad3A{ub}
--
e81
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m86
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
p1
p1
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c1 : 1
m155666*m3961*0.1
nodelay
--
0
PMID: 15876435, 9851930 The most compelling evidence that LPS was acting through TLR4 came from studies on a strain of mice called the C3H/HeJ mice. These mice have a point mutation in the gene encoding TLR4 that renders them hyporesponsive to LPS challenge.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c161 : 1
stoichiometry:c29 : 1
m17*m18*0.1
nodelay
--
0
PMID: 15876435, 14625308 IRAK-4 is thought to function upstream of IRAK-1 and has been shown to phosphorylate IRAK-1 in vitro. PMID: 15876435 A splice variant of MyD88, termed MyD88s, also inhibits LPS/IL-1 induced NF-¦ÊB activity by preventing the association of IRAK-1 with IRAK-4 and the subsequent activation of IRAK-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c162 : 1
stoichiometry:c31 : 1
m19*0.1
nodelay
--
0
PMID: 15876435, 14625308 IRAK-4 is thought to function upstream of IRAK-1 and has been shown to phosphorylate IRAK-1 in vitro. PMID: 15876435 A splice variant of MyD88, termed MyD88s, also inhibits LPS/IL-1 induced NF-¦ÊB activity by preventing the association of IRAK-1 with IRAK-4 and the subsequent activation of IRAK-1.
p12
p12
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c32 : 1
stoichiometry:c167 : 1
stoichiometry:c34 : 1
m183*m83*0.1
nodelay
--
0
PMID: 15876435, 8837778 Upon activation, IRAK-1 engages with tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6), a member of the TRAF family of proteins. PMID: 15876435 IRAK-M, a kinase inactive IRAK family member, prevents the disssociation of IRAK-1 from MyD88 and the subsequent association of IRAK-1 with the downstream adaptor TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c36 : 1
m21*0.1
nodelay
--
0
PMID: 15876435, 11057907 TRAF6 undergoes ubiquitination following cell stimulation and that TRAF6 itself is a ubiquitin ligase.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c38 : 1
m24*0.1
nodelay
--
0
PMID: 15876435, 11460167 Once ubiquitinated, TRAF6 activates IKK through a TAK1-TAB1-TAB2 kinase complex.
p15
p15
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c42 : 1
stoichiometry:c41 : 1
m207*m23*0.1
nodelay
--
0
PMID: 15876435 Once activated, TAK1 phosphorylates the activation loop of IKK¦Â, thereby activating the IKK complex and the pleiotropic transcription factor, NF-¦ÊB.
p16
p16
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c45 : 1
stoichiometry:c44 : 1
m27*m25*0.1
nodelay
--
0
PMID: 15876435 Once activated, TAK1 phosphorylates the activation loop of IKK¦Â, thereby activating the IKK complex and the pleiotropic transcription factor, NF-¦ÊB.
p17
p17
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c47 : 1
m3613*m23*0.1
nodelay
--
0
PMID: 15876435, 11460167 TAK1 also phosphorylates MKK6 and 7, which in turn activate the p38 and JNK kinase pathways, respectively.
p18
p18
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c51 : 1
stoichiometry:c50 : 1
m1831*m23*0.1
nodelay
--
0
PMID: 15876435, 11460167 TAK1 also phosphorylates MKK6 and 7, which in turn activate the p38 and JNK kinase pathways, respectively.
p19
p19
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c54 : 1
stoichiometry:c53 : 1
m30*m28*0.1
nodelay
--
0
PMID: 15876435, 11460167 TAK1 also phosphorylates MKK6 and 7, which in turn activate the p38 and JNK kinase pathways, respectively.
p2
p2
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1
m3961*m2254*0.1
nodelay
--
0
PMID: 15876435, 15790348 It later emerged that TLR4 is also a receptor for endogenous ligands such as fibrinogen, heat shock proteins (HSP 60 and HSP 70), fibronectins and hyaluronic acid.
p20
p20
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c57 : 1
stoichiometry:c56 : 1
m32*m29*0.1
nodelay
--
0
PMID: 15876435, 11460167 TAK1 also phosphorylates MKK6 and 7, which in turn activate the p38 and JNK kinase pathways, respectively.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c59 : 1
stoichiometry:c60 : 1
m19005*m14*0.1
nodelay
--
0
PMID: 15876435 TRAM, like Mal, acts as a bridge to couple TRIF to TLR4 and is absolutely required for TLR4 mediated responses.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c62 : 1
stoichiometry:c63 : 1
m34*m18998*0.1
nodelay
--
0
PMID: 15876435 TRAM, like Mal, acts as a bridge to couple TRIF to TLR4 and is absolutely required for TLR4 mediated responses.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c65 : 1
stoichiometry:c66 : 1
m35*m183*0.1
nodelay
--
0
PMID: 15876435 The N-terminus of TRIF contains binding sites for TRAF6 and the non-canonical kinases IKKi and TBK1, the TIR domain presumably tethers TRIF to its binding partner TRAM and finally the C-terminus of TRIF contains a RIP-1 binding site.
p24
p24
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c67 : 1
stoichiometry:c70 : 1
m1599*m3902*m35*0.1
nodelay
--
0
PMID: 15876435 The N-terminus of TRIF contains binding sites for TRAF6 and the non-canonical kinases IKKi and TBK1, the TIR domain presumably tethers TRIF to its binding partner TRAM and finally the C-terminus of TRIF contains a RIP-1 binding site.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c71 : 1
stoichiometry:c73 : 1
m38*m36*0.1
nodelay
--
0
PMID: 15876435 The N-terminus of TRIF contains binding sites for TRAF6 and the non-canonical kinases IKKi and TBK1, the TIR domain presumably tethers TRIF to its binding partner TRAM and finally the C-terminus of TRIF contains a RIP-1 binding site.
p26
p26
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c76 : 1
stoichiometry:c75 : 1
m27*m39*0.1
nodelay
--
0
PMID: 15876435 Both TRAF6 and RIP-1 are thought to mediate TRIF induced NF-¦ÊB activation whereas IKKi and TBK1 are required for TRIF-induced IRF-3 activation.
p27
p27
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c77 : 1
stoichiometry:c79 : 1
stoichiometry:c78 : 1
m977*m37*0.1
nodelay
--
0
PMID: 15876435 Both TRAF6 and RIP-1 are thought to mediate TRIF induced NF-¦ÊB activation whereas IKKi and TBK1 are required for TRIF-induced IRF-3 activation.
p28
p28
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c81 : 1
stoichiometry:c82 : 1
m3964*m3963*0.1
nodelay
--
0
PMID: 15876435 The ability of TLR2 to recognize such a wide range of compounds has been attributed to the ability of TLR2 to heterodimerize with other TLRs, namely TLR1 and TLR6.
p29
p29
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c84 : 1
stoichiometry:c85 : 1
m3987*m3964*0.1
nodelay
--
0
PMID: 15876435 The ability of TLR2 to recognize such a wide range of compounds has been attributed to the ability of TLR2 to heterodimerize with other TLRs, namely TLR1 and TLR6.
p3
p3
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
m3961*m4645*0.1
nodelay
--
0
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1
m41*m43*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c91 : 1
m45*m42*0.1
nodelay
--
0
PMID: 15876435, 12077222, 11431423 The association of TLR2 with TLR1 permits the recognition of triacyl lipopeptides whereas TLR2/TLR6 heterodimers recognize diacyl lipopeptides.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c93 : 1
m46*0.1
nodelay
--
0
PMID: 15876435, 11101877 Biochemical studies with heat-killed Staphylococcus aureus (HKSA) have demonstrated that phosphorylation of TLR2 on specific tyrosine residues facilitates the recruitment of PI3K, an effector of the small G-protein, Rac-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c95 : 1
stoichiometry:c96 : 1
m47*m48*0.1
nodelay
--
0
PMID: 15876435, 11101877 Biochemical studies with heat-killed Staphylococcus aureus (HKSA) have demonstrated that phosphorylation of TLR2 on specific tyrosine residues facilitates the recruitment of PI3K, an effector of the small G-protein, Rac-1. PMID: 15876435 The p85 subunit of PI3K binds to phospho-tyrosine residues via a src-homology domain.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c98 : 1
stoichiometry:c99 : 1
m49*m146*0.1
nodelay
--
0
PMID: 15876435 The p85 subunit of PI3K binds to phospho-tyrosine residues via a src-homology domain. Phosphorylation of TLR2 by an as yet unidentified kinase induces the formation of an active TLR2?Rac1?PI3K complex.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c101 : 1
stoichiometry:c102 : 1
m16*m48*0.1
nodelay
--
0
PMID: 15876435 PI3K does not bind directly to TLR4 but rather interacts with TLR4 through MyD88.
p36
p36
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c103 : 1
stoichiometry:c104 : 1
stoichiometry:c180 : 1
m3966*m6485*0.1
nodelay
--
0
PMID: 15876435, 11323673 TLR5 recognizes flagellin, a monomeric constituent of bacterial flagella.
p37
p37
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c107 : 1
stoichiometry:c106 : 1
m3965*m119368*0.1
nodelay
--
0
PMID: 15876435 TLR3 is highly expressed in macrophages, dendritic cells and epithelial cells and induces the expression of IFN-¦Â following exposure to double stranded (d/s) RNA.
p38
p38
cso30:i:ME_GeneExpression
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c108 : 1
m19314*0.1
nodelay
--
0
PMID: 15876435 TLR3 is highly expressed in macrophages, dendritic cells and epithelial cells and induces the expression of IFN-¦Â following exposure to double stranded (d/s) RNA.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c115 : 1
stoichiometry:c111 : 1
m19940*m72*0.1
nodelay
--
0
PMID: 15876435 TLRs 7 and 9 are expressed in a subset of DCs called plasmacytoid DCs or pre-DC2 cells. Exposure of these cells to ssRNA or DNA from viral genomes results in the secretion of large amounts of IFN-alpha.
p4
p4
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1
m3961*m5956*0.1
nodelay
--
0
PMID: 15876435, 15790348 It later emerged that TLR4 is also a receptor for endogenous ligands such as fibrinogen, heat shock proteins (HSP 60 and HSP 70), fibronectins and hyaluronic acid.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c114 : 1
stoichiometry:c113 : 1
m19828*m71*0.1
nodelay
--
0
PMID: 15876435 TLRs 7 and 9 are expressed in a subset of DCs called plasmacytoid DCs or pre-DC2 cells. Exposure of these cells to ssRNA or DNA from viral genomes results in the secretion of large amounts of IFN-alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c116 : 1
m65*0.1
nodelay
--
0
PMID: 15876435 TLRs 7 and 9 are expressed in a subset of DCs called plasmacytoid DCs or pre-DC2 cells. Exposure of these cells to ssRNA or DNA from viral genomes results in the secretion of large amounts of IFN-alpha.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c119 : 1
stoichiometry:c118 : 1
m70*0.1
nodelay
--
0
PMID: 15876435 TLRs 7 and 9 are expressed in a subset of DCs called plasmacytoid DCs or pre-DC2 cells. Exposure of these cells to ssRNA or DNA from viral genomes results in the secretion of large amounts of IFN-alpha.
p43
p43
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c121 : 1
stoichiometry:c138 : 1
stoichiometry:c139 : 1
stoichiometry:c122 : 1
m18998*m78*m48*0.1
nodelay
--
0
PMID: 15876435 TLR3 functions independently of MyD88 requiring only the adaptor TRIF to transmit signals to the nucleus. PMID: 15876435 phosphorylated TLR3 recruits both TRIF and PI3K.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c123 : 1
stoichiometry:c124 : 1
stoichiometry:c125 : 1
m74*m38*0.1
nodelay
--
0
PMID: 15876435 TLR3 can activate NF-¦ÊB to some extent and this is thought to be mediated by the interaction of RIP1 with TRIF.
p45
p45
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c128 : 1
stoichiometry:c127 : 1
m27*m75*0.1
nodelay
--
0
PMID: 15876435 TLR3 can activate NF-¦ÊB to some extent and this is thought to be mediated by the interaction of RIP1 with TRIF.
p46
p46
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c130 : 1
stoichiometry:c131 : 1
stoichiometry:c136 : 1
stoichiometry:c132 : 1
m74*m3902*m1599*m77*0.1
nodelay
--
0
PMID: 15876435 As described for TLR4, TRIF also recruits the kinases TBK1 and IKKi to activate IRF-3. PMID: 15876435 TANK homolog, NAP1 (NF-¦ÊB-activating kinase (NAK)-associated protein 1) that forms a functional complex with TBK1 and IKKi rather than TANK itself.
p47
p47
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c133 : 1
stoichiometry:c135 : 1
stoichiometry:c134 : 1
m977*m76*0.1
nodelay
--
0
PMID: 15876435 As described for TLR4, TRIF also recruits the kinases TBK1 and IKKi to activate IRF-3. PMID: 15876435 TRIF in turn recruits the kinase complex NAP1/IKKi /TBK1 leading to partial IRF3 phosphorylation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c120 : 1
stoichiometry:c137 : 1
m19314*0.1
nodelay
--
0
PMID: 15876435 phosphorylated TLR3 recruits both TRIF and PI3K.
p49
p49
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c141 : 1
stoichiometry:c142 : 1
stoichiometry:c144 : 1
stoichiometry:c143 : 1
m980*m1572*m183*m70*0.1
nodelay
--
0
PMID: 15876435, 15361868 MyD88 and TRAF6 directly associate with IRF7 to induce IFN-alpha following stimulation of cells with ligands for TLR7 and TLR9.
p5
p5
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c14 : 1
m2341*m3961*0.1
nodelay
--
0
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c146 : 1
stoichiometry:c145 : 1
m79*0.1
nodelay
--
0
PMID: 15876435, 15361868 MyD88 and TRAF6 directly associate with IRF7 to induce IFN- alpha following stimulation of cells with ligands for TLR7 and TLR9.
p51
p51
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c147 : 1
stoichiometry:c149 : 1
stoichiometry:c148 : 1
m980*m18*0.1
nodelay
--
0
PMID: 15876435, 15361868 IRAK-1 also participates in the activation of IRF-7 possibly through direct phosphorylation as suggested by in vitro kinase assays.
p52
p52
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c150 : 1
stoichiometry:c152 : 1
stoichiometry:c151 : 1
m980*m3902*0.1
nodelay
--
0
PMID: 15876435, 12692549 It should be noted however that TBK1 and IKKi have also been shown to phosphorylate IRF-7.
p53
p53
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c153 : 1
stoichiometry:c155 : 1
stoichiometry:c154 : 1
m980*m1599*0.1
nodelay
--
0
PMID: 15876435, 12692549 It should be noted however that TBK1 and IKKi have also been shown to phosphorylate IRF-7.
p54
p54
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c157 : 1
stoichiometry:c158 : 1
stoichiometry:c159 : 1
stoichiometry:c160 : 1
m65*m979*m1572*m183*0.1
nodelay
--
0
PMID: 15876435, 15695821, 15665823 IRF5 complexes with both MyD88 and TRAF6 and IRF-5, like IRF-7, is activated by TLR7 and TLR8.
p55
p55
cso30:i:ME_Dissociation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c166 : 1
stoichiometry:c164 : 1
stoichiometry:c165 : 1
m20*0.1
nodelay
--
0
PMID: 15876435 IRAK-M, a kinase inactive IRAK family member, prevents the disssociation of IRAK-1 from MyD88 and the subsequent association of IRAK-1 with the downstream adaptor TRAF6.
p56
p56
cso30:i:ME_Deubiquitination
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c170 : 1
stoichiometry:c168 : 1
stoichiometry:c169 : 1
m22*m1585*0.1
nodelay
--
0
PMID: 15876435, 15361868 the deubiquitinating enzyme, A20, returns TRAF6 to an unmodified state and in doing so terminates TLR responses.
p57
p57
cso30:i:ME_UnknownDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c171 : 1
stoichiometry:c173 : 1
stoichiometry:c172 : 1
m3961*m85*0.1
nodelay
--
0
PMID: 15876435, 15107846 Triad3A, a novel RING-type E3 ubiquitin-ligase was recently shown to promote the degradation of TLR3, TLR4, TLR5 and TLR9 but not TLR2.
p58
p58
cso30:i:ME_UnknownDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c176 : 1
stoichiometry:c175 : 1
m3965*m85*0.1
nodelay
--
0
PMID: 15876435, 15107846 Triad3A, a novel RING-type E3 ubiquitin-ligase was recently shown to promote the degradation of TLR3, TLR4, TLR5 and TLR9 but not TLR2.
p59
p59
cso30:i:ME_UnknownDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c177 : 1
stoichiometry:c179 : 1
stoichiometry:c178 : 1
m19828*m85*0.1
nodelay
--
0
PMID: 15876435, 15107846 Triad3A, a novel RING-type E3 ubiquitin-ligase was recently shown to promote the degradation of TLR3, TLR4, TLR5 and TLR9 but not TLR2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c20 : 1
m14*m6810*0.1
nodelay
--
0
PMID: 15876435 Unlike MyD88, Mal is not required for IL-1 signaling and its role in TLR4 signaling appears to be structural one, acting as a bridge to couple MyD88 to TLR4.
p60
p60
cso30:i:ME_UnknownDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c181 : 1
stoichiometry:c183 : 1
stoichiometry:c182 : 1
m3966*m85*0.1
nodelay
--
0
PMID: 15876435, 15107846 Triad3A, a novel RING-type E3 ubiquitin-ligase was recently shown to promote the degradation of TLR3, TLR4, TLR5 and TLR9 but not TLR2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c184 : 1
stoichiometry:c185 : 1
m85*0.1
nodelay
--
0
PMID: 15876435 Triad3A was also found to undergo autoubiqutination similar to TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
m5*0.1
nodelay
--
0
PMID: 15876435 Following exposure of cells to LPS, TLR4 homodimerizes and recruits two sets of adaptor molecules.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
m15*m1572*0.1
nodelay
--
0
PMID: 15876435 Unlike MyD88, Mal is not required for IL-1 signaling and its role in TLR4 signaling appears to be structural one, acting as a bridge to couple MyD88 to TLR4.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c26 : 1
m16*m17258*0.1
nodelay
--
0
PMID: 15876435 MyD88 differs from Mal in that it also possesses an N-terminal death domain. This domain serves to recruit members of the IL-1 receptor associated kinase (IRAK) family of which there are four. PMID: 15876435, 14625308 IRAK-4 is thought to function upstream of IRAK-1 and has been shown to phosphorylate IRAK-1 in vitro.
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--