Original Literature | Model OverView |
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Publication
Title
Innate immune responses during infection.
Affiliation
Department of Immunology, The Scripps Research Institute, 10550 North TorreyPines Road, La Jolla, CA 92037, USA.
Abstract
The innate immune system senses bacteria in the environment and defends againstinfection. Here we will discuss two types of sensor protein families. The plasmamembrane receptors that comprise the Toll-like receptor (TLRs) family and theintracellular proteins termed NOD1 and NOD2. These proteins directly bindbacterial products such as lipopolysaccharides (LPS), peptidoglycan fragments,bacterial DNA, and receptor binding leads to intracellular signaling and geneexpression. TLR signaling involves members of the MyD88 family of adaptorproteins. In contrast NOD1 or NOD2 utilize pathways that do not depend on theMyD88 family members.
PMID
15576198
|
Entity
NF-kappaB
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m30
10
infinite
0
TRANSPATH | MO000000058 |
--
--
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
--
TLR2: TLR6
--
e12
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m12
0
infinite
0
--
diacylated lipopeptides
--
e13
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m13
0
infinite
0
--
diacylated lipoproteins: TLR2: TLR1
--
e14
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m14
0
infinite
0
--
triacylated lipoproteins: TLR2: TLR6
--
e15
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m15
0
infinite
0
--
triacylated lipoproteins
--
e16
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m16
0
infinite
0
--
csml-variable:Double
m17
0
infinite
0
--
CpG DNA: TLR9
--
e18
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m18
0
infinite
0
--
loxoribine
--
e19
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
imadazole quinoline
--
e20
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m20
0
infinite
0
--
loxoribine: TLR7
--
e21
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m21
0
infinite
0
--
imadazole quinoline: TLR8
--
e22
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m22
0
infinite
0
--
flagellin: TLR9
--
e23
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m23
0
infinite
0
--
LPS:CD14: TLR4: MD-2: MyD88
--
e24
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m24
0
infinite
0
--
Mal
--
e25
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m25
0
infinite
0
--
LPS:CD14: TLR4: MD-2: MyD88: TIRAP: Mal
--
e26
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m26
0
infinite
0
--
LPS:CD14: TLR4: MD-2: TRIF
--
e27
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m27
0
infinite
0
--
IRAK-4 {activated}
--
e28
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m28
10
infinite
0
TRANSPATH | MO000039077 |
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
NF-kappaB {activated}
--
e30
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m31
10
infinite
0
TRANSPATH | MO000000058 |
--
PGN: Nod1
--
e31
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m32
0
infinite
0
--
PGN: Nod2
--
e32
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m33
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
CD14: TLR4: MD-2
--
e5
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
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
--
LPS:CD14: TLR4: MD-2
--
e6
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
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
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m5*m155666*0.1
nodelay
--
0
PMID: 15576198 the lipopolysaccharide (LPS) receptor is made up of at least three proteins, CD14, MD-2 and TLR4.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c29 : 1
stoichiometry:c30 : 1
m6*m1572*0.1
nodelay
--
0
PMID: 15576198, 12872135 MyD88 also contains a TIR domain, which associates with the TIR domain of the TLRs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1
stoichiometry:c34 : 1
m6810*m25*m24*0.1
nodelay
--
0
PMID: 15576198 A family of proteins with TIR domains that are structurally and functionally related to MyD88 has been identified. This family includes proteins named TIRAP and TRIF.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c35 : 1
stoichiometry:c37 : 1
m18998*m6*0.1
nodelay
--
0
PMID: 15576198 A family of proteins with TIR domains that are structurally and functionally related to MyD88 has been identified. This family includes proteins named TIRAP and TRIF.
p13
p13
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c40 : 1
m26*m17258*0.1
nodelay
--
0
PMID: 15576198 A number of studies indicates roles of TRAF6 and members of the IRAK family (interleukin-1-associated receptor kinase), most notably IRAK-4, downstream of MyD88.
p14
p14
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c43 : 1
stoichiometry:c42 : 1
m183*m28*0.1
nodelay
--
0
PMID: 15576198 A number of studies indicates roles of TRAF6 and members of the IRAK family (interleukin-1-associated receptor kinase), most notably IRAK-4, downstream of MyD88.
p15
p15
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c46 : 1
stoichiometry:c45 : 1
m30*m29*0.1
nodelay
--
0
PMID: 15576198 This highly conserved pathway is linked to activation of the NF-kappaB pathway.
p16
p16
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c48 : 1
stoichiometry:c49 : 1
m4923*m155701*0.1
nodelay
--
0
PMID: 15576198, 12791997, 12796777 both proteins recognize monomeric components of peptidoglycan.
p17
p17
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c52 : 1
m155701*m4947*0.1
nodelay
--
0
PMID: 15576198, 12791997, 12796777 both proteins recognize monomeric components of peptidoglycan.
p18
p18
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c57 : 1
stoichiometry:c59 : 1
stoichiometry:c54 : 1
m30*m32*m2684*0.1
nodelay
--
0
PMID: 15576198 Binding of the cognate ligants to NOD1 or NOD2 leads to activation of NF-kappaB by a mechanism requiring the presence of the kinase known as RICK (Rip2).
p19
p19
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c56 : 1
m30*m33*m2684*0.1
nodelay
--
0
PMID: 15576198 Binding of the cognate ligants to NOD1 or NOD2 leads to activation of NF-kappaB by a mechanism requiring the presence of the kinase known as RICK (Rip2).
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
m3964*m3963*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 TLR2?TLR1 heterodimers recognize diacylated lipopeptides whereas TLR2?TLR6 heterodimers recognize triacylated lipopeptides.
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
m3987*m3964*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 TLR2?TLR1 heterodimers recognize diacylated lipopeptides whereas TLR2?TLR6 heterodimers recognize triacylated lipopeptides.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1
m13*m11*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 TLR2?TLR1 heterodimers recognize diacylated lipopeptides whereas TLR2?TLR6 heterodimers recognize triacylated lipopeptides.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1
m12*m16*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 TLR2?TLR1 heterodimers recognize diacylated lipopeptides whereas TLR2?TLR6 heterodimers recognize triacylated lipopeptides.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c18 : 1
m17*m19828*0.1
nodelay
--
0
PMID: 15576198, 12467249 It has been shown that TLR9, receptor for bacterial DNA containing sequences of non-methylated CpG sequences, is localized and acts in an intracellular compartment.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c21 : 1
m19940*m19*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 More recently, synthetic nucleoside analogues loxoribine and imadazole quinolines have been identified as ligands for TLR7 and TLR8, respectively.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1
m19823*m20*0.1
nodelay
--
0
PMID: 15576198, 12524386, 14498823, 12960260 More recently, synthetic nucleoside analogues loxoribine and imadazole quinolines have been identified as ligands for TLR7 and TLR8, respectively.
p9
p9
cso30:i:ME_Binding
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c27 : 1
m6485*m3966*0.1
nodelay
--
0
PMID: 15576198, 10963608 Biochemical studies have shown the direct binding of LPS-TLR4 and bacterial flagellin protein-TLR5.
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: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:InputAssociation
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: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: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,
--