Original Literature | Model OverView |
---|---|
Publication
Title
LPS induction of gene expression in human monocytes.
Affiliation
Departments of Immunology, C-204, The Scripps Research Institute, 10550 NorthTorrey Pines Road, La Jolla, CA 92037, USA.
Abstract
Lipopolysaccharide (LPS [endotoxin]) is the principal component of the outermembrane of Gram-negative bacteria. Recent studies have elucidated how LPS isrecognized by monocytes and macrophages of the innate immune system. Humanmonocytes are exquisitely sensitive to LPS and respond by expressing manyinflammatory cytokines. LPS binds to LPS-binding protein (LBP) in plasma and isdelivered to the cell surface receptor CD14. Next, LPS is transferred to thetransmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessoryprotein MD2. LPS stimulation of human monocytes activates several intracellularsignaling pathways that include the IkappaB kinase (IKK)-NF-kappaB pathway andthree mitogen-activated protein kinase (MAPK) pathways: extracellularsignal-regulated kinases (ERK) 1 and 2, c-Jun N-terminal kinase (JNK) and p38.These signaling pathways in turn activate a variety of transcription factorsthat include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate theinduction of many genes encoding inflammatory mediators.
PMID
11257452
|
Entity
LPS
--
e1
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m1
0
infinite
0
--
TLR4:MD2
--
e10
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m10
0
infinite
0
PubMed | 11257452 |
--
csml-variable:Double
m99
0
infinite
0
--
csml-variable:Double
m100
0
infinite
0
--
csml-variable:Double
m101
0
infinite
0
--
csml-variable:Double
m102
0
infinite
0
--
csml-variable:Double
m103
0
infinite
0
--
csml-variable:Double
m104
0
infinite
0
--
csml-variable:Double
m105
0
infinite
0
--
csml-variable:Double
m106
0
infinite
0
--
csml-variable:Double
m107
0
infinite
0
--
csml-variable:Double
m108
0
infinite
0
--
csml-variable:Double
m109
0
infinite
0
--
csml-variable:Double
m110
0
infinite
0
--
csml-variable:Double
m111
0
infinite
0
--
csml-variable:Double
m112
0
infinite
0
--
csml-variable:Double
m12
0
infinite
0
--
csml-variable:Double
m13
0
infinite
0
--
csml-variable:Double
m14
0
infinite
0
--
csml-variable:Double
m15
0
infinite
0
--
csml-variable:Double
m16
0
infinite
0
--
csml-variable:Double
m17
0
infinite
0
--
TAK1
--
e18
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
csml-variable:Double
m18
0
infinite
0
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
csml-variable:Double
m20
0
infinite
0
--
csml-variable:Double
m21
0
infinite
0
--
csml-variable:Double
m22
0
infinite
0
--
csml-variable:Double
m23
0
infinite
0
--
csml-variable:Double
m24
0
infinite
0
--
p50:p65:Ikappa-Balpha{p}
--
e25
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m25
0
infinite
0
--
csml-variable:Double
m26
0
infinite
0
--
protein reminant of Ikappa-Balpha
--
e27
cso30:c:EntityBiological
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m27
0
infinite
0
--
--
e28
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m28
0
infinite
0
--
csml-variable:Double
m29
0
infinite
0
--
csml-variable:Double
m30
0
infinite
0
--
csml-variable:Double
m31
0
infinite
0
--
csml-variable:Double
m32
0
infinite
0
--
csml-variable:Double
m33
0
infinite
0
--
csml-variable:Double
m34
0
infinite
0
--
csml-variable:Double
m35
0
infinite
0
--
--
e36
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m36
0
infinite
0
--
csml-variable:Double
m37
0
infinite
0
--
csml-variable:Double
m38
0
infinite
0
--
csml-variable:Double
m39
0
infinite
0
--
csml-variable:Double
m40
0
infinite
0
--
csml-variable:Double
m41
0
infinite
0
--
csml-variable:Double
m42
0
infinite
0
--
csml-variable:Double
m43
0
infinite
0
--
csml-variable:Double
c-fos:c-jun
0
infinite
0
--
csml-variable:Double
m44
0
infinite
0
--
--
e46
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m45
0
infinite
0
--
csml-variable:Double
m46
0
infinite
0
--
csml-variable:Double
m47
0
infinite
0
--
csml-variable:Double
m48
0
infinite
0
--
CD14
--
e5
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m5
0
infinite
0
Entrez Gene | 929, 60350, 12475 |
PubMed | 11257452 |
UniProt | P08571 |
--
csml-variable:Double
m49
0
infinite
0
--
csml-variable:Double
m50
0
infinite
0
--
p38{active}
--
e52
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m51
0
infinite
0
--
c-jun:ATF2
--
e53
cso30:c:Complex
cso30:i:CC_NuclearChromosome
--
csml-variable:Double
m52
0
infinite
0
--
c-jun{p}:ATF2{p}
--
e54
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m53
0
infinite
0
--
csml-variable:Double
m54
0
infinite
0
--
csml-variable:Double
m56
0
infinite
0
--
csml-variable:Double
m57
0
infinite
0
--
csml-variable:Double
m58
0
infinite
0
--
CD14:LPS
--
e6
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m6
0
infinite
0
PubMed | 11257452 |
--
csml-variable:Double
m59
0
infinite
0
--
csml-variable:Double
m60
0
infinite
0
--
csml-variable:Double
m61
0
infinite
0
--
csml-variable:Double
m62
0
infinite
0
--
csml-variable:Double
m63
0
infinite
0
--
ELK1{p}:SRF{p}
--
e65
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m64
0
infinite
0
--
CREB:ATF1
--
e66
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m65
0
infinite
0
--
CREB{p}:ATF1{p}
--
e67
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m66
0
infinite
0
--
--
e68
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m67
0
infinite
0
--
--
e69
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m68
0
infinite
0
--
--
e70
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m69
0
infinite
0
--
--
e71
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m70
0
infinite
0
--
--
e72
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m71
0
infinite
0
--
--
e73
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m72
0
infinite
0
--
--
e74
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m73
0
infinite
0
--
--
e75
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m74
0
infinite
0
--
--
e76
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m75
0
infinite
0
--
--
e77
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m76
0
infinite
0
--
--
e78
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m77
0
infinite
0
--
--
e79
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m78
0
infinite
0
--
TLR4
--
e8
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
csml-variable:Double
m8
0
infinite
0
Entrez Gene | 7099, 21898, 29260 |
PubMed | 11257452 |
UniProt | O00206 |
--
--
e80
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m79
0
infinite
0
--
--
e81
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m80
0
infinite
0
--
--
e82
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m81
0
infinite
0
--
--
e83
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m82
0
infinite
0
--
--
e84
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m83
0
infinite
0
--
csml-variable:Double
m84
0
infinite
0
--
genistein
--
e86
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m85
0
infinite
0
--
csml-variable:Double
m86
0
infinite
0
--
csml-variable:Double
m87
0
infinite
0
--
csml-variable:Double
m88
0
infinite
0
--
LPS: TLR4:MD2
--
e9
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
csml-variable:Double
m9
0
infinite
0
PubMed | 11257452 |
--
csml-variable:Double
m89
0
infinite
0
--
csml-variable:Double
m90
0
infinite
0
--
csml-variable:Double
m91
0
infinite
0
--
csml-variable:Double
m92
0
infinite
0
--
csml-variable:Double
m93
0
infinite
0
--
csml-variable:Double
m94
0
infinite
0
--
csml-variable:Double
m95
0
infinite
0
--
csml-variable:Double
m96
0
infinite
0
--
U0126
--
e98
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
csml-variable:Double
m97
0
infinite
0
--
dexamethasone
--
e99
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m98
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1
m3*m1*0.1
nodelay
--
0
PubMed | 11257452 |
PMID: 11257452 LPS binds to the serum protein LBP and is transferred to the CD14 at the cell surface. PMID: 11257452 LPS and LPS-containing particles (including intact bacteria) form complexes with a plasma protein known as LPS-binding protein (LBP).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c32 : 1
stoichiometry:c31 : 1
m23*m22*0.1
nodelay
--
0
PMID: 11257452 TAK1?TAB2 and MEKK1?ECSIT complexes phosphorylate IKK¦Â.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c33 : 1
stoichiometry:c34 : 1
m24*m84*0.1
nodelay
--
0
PMID: 11257452 IKK¦Â phosphorylates I¦ÊBs.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c37 : 1
stoichiometry:c38 : 1
m25*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c120 : 1
stoichiometry:c40 : 1
m29*m87*0.1
nodelay
--
0
PMID: 11257452 The PI3K?Akt pathway phosphorylates and activates p65 via an unknown kinase.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1
m30*0.1
nodelay
--
0
PMID: 11257452 Degradation of I¦ÊBs permits nuclear translocation of NF-¦ÊB/Rel complexes, such as p50/p65.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c44 : 1
m88*0.1
nodelay
--
0
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS. PMID: 11257452, 78 The N-terminal region (amino acids 1-450) of CBP, a protein highly homologous to p300, specifically interacts with the C-terminal region (amino acids 286-551) of p65 both in vitro and in vivo.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c47 : 1
stoichiometry:c46 : 1
m33*m9*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c50 : 1
stoichiometry:c49 : 1
m34*m32*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c54 : 1
stoichiometry:c53 : 1
m38*m9*0.1
nodelay
--
0
PMID: 11257452, 8610116 LPS stimulation of THP-1 cells and RAW 264.7 cells rapidly activates the JNK pathway. PMID: 11257452, 9891090, 10207617, 9096336 The MAPKKs, MKK4, and MKK7 are direct activators of JNK.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c57 : 1
stoichiometry:c56 : 1
m40*m37*0.1
nodelay
--
0
PMID: 11257452 LPS stimulation of THP-1 cells and RAW 264.7 cells rapidly activates the JNK pathway. The MAPKKs, MKK4, and MKK7 are direct activators of JNK.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1
stoichiometry:c104 : 1
m4*m5*0.1
nodelay
--
0
PubMed | 11257452 |
PMID:11257452 LPS binds to the serum protein LBP and is transferred to the CD14 at the cell surface.
p20
p20
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c138 : 1
stoichiometry:c59 : 1
m41*m39*0.1
nodelay
--
0
PMID: 11257452 LPS stimulation of THP-1 cells and RAW 264.7 cells rapidly activates the JNK pathway. The MAPKKs, MKK4, and MKK7 are direct activators of JNK. PMID: 11257452, 9343388 The immunosuppressant dexamethasone reduced LPS-induced translation of TNF¦Á mRNA by selectively inhibiting the JNK pathway.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c81 : 1
stoichiometry:c80 : 1
m44*m51*0.1
nodelay
--
0
PMID: 11257452, 9687510 p38 also phosphorylates numerous downstream kinases, including MNK1/2, MAPKAPK2 (MK2), MSK1, and PRAK, which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c63 : 1
stoichiometry:c62 : 1
c-fos:c-jun*m42*0.1
nodelay
--
0
PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c107 : 1
stoichiometry:c68 : 1
m46*m9*0.1
nodelay
--
0
PMID: 11257452 MAPKKKs involved in the p38 signaling cascade include protein kinase RNA-regulated (PKR).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c72 : 1
stoichiometry:c71 : 1
m48*m47*0.1
nodelay
--
0
PMID: 11257452 The MAPKKs involved in p38 activation include the dual specificity kinases MKK3 and MKK6.
p26
p26
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c75 : 1
stoichiometry:c139 : 1
stoichiometry:c170 : 1
stoichiometry:c74 : 1
m50*m49*m39*0.1
nodelay
--
0
PMID: 11257452 The MAPKKs involved in p38 activation include the dual specificity kinases MKK3 and MKK6. PMID: 11257452, 7839144 There is some evidence that MKK4 also phosphorylates the p38. PMID: 11257452, 7997261 One of these compounds, SB203580, specifically inhibited p38 activation and reduced LPS induction of IL-1 and TNFa expression without affecting the mRNA accumulation [149].
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c66 : 1
stoichiometry:c77 : 1
m52*m42*0.1
nodelay
--
0
PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c102 : 1
stoichiometry:c101 : 1
m65*m54*0.1
nodelay
--
0
PMID: 11257452 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c9 : 1
stoichiometry:c10 : 1
stoichiometry:c105 : 1
m6*m10*0.1
nodelay
--
0
PMID: 11257452 LPS binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14. Next, LPS is transferred to the transmembrane signaling receptor toll-like receptor 4 (TLR4) and its accessory protein MD2. PMID: 11257452 TLR4-MD2 complex functions as the LPS signaling receptor on the surface of monocytes. PMID: 11257452 LPS then interacts with the signaling receptor TLR4 and the accessory protein MD-2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c106 : 1
stoichiometry:c83 : 1
m55*m9*0.1
nodelay
--
0
PMID: 11257452 LPS activation of tyrosine kinases leads to activation of the MEK?ERK1/2 pathway in a Raf-1-dependent manner.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c87 : 1
stoichiometry:c86 : 1
m57*m56*0.1
nodelay
--
0
PMID: 11257452 LPS activation of tyrosine kinases leads to activation of the MEK?ERK1/2 pathway in a Raf-1-dependent manner.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c90 : 1
stoichiometry:c136 : 1
stoichiometry:c89 : 1
m59*m58*0.1
nodelay
--
0
PMID: 11257452 LPS activation of tyrosine kinases leads to activation of the MEK?ERK1/2 pathway in a Raf-1-dependent manner. PMID: 11257452, 99 Inhibition of MEK in monocytes by U0126 reduced LPS induction of several inflammatory cytokines, including IL-1, IL-8, and TNF¦Á, as well as prostaglandin E2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c93 : 1
stoichiometry:c92 : 1
m61*m60*0.1
nodelay
--
0
PMID: 11257452 LPS activation of tyrosine kinases leads to activation of the MEK?ERK1/2 pathway in a Raf-1-dependent manner.
p34
p34
cso30:i:ME_Phosphorylation
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c96 : 1
stoichiometry:c43 : 1
stoichiometry:c95 : 1
m63*m62*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452, 10417144 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS.
p37
p37
cso30:i:ME_Phosphorylation
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c98 : 1
stoichiometry:c115 : 1
stoichiometry:c84 : 1
m63*m51*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452, 10417144 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1. PMID: 11257452, 8622669 p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1, CHOP, MEF2C, and Sap1a.
p38
p38
cso30:i:ME_Phosphorylation
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c110 : 1
stoichiometry:c116 : 1
stoichiometry:c109 : 1
m63*m42*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452, 10417144 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c112 : 1
stoichiometry:c111 : 1
m52*m51*0.1
nodelay
--
0
PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452, 9422727 p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c7 : 1
stoichiometry:c12 : 1
m7*m8*0.1
nodelay
--
0
PMID: 11257452 MD-2 physically associated with TLR4 in a similar manner to MD-1 binding to RP105.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c113 : 1
stoichiometry:c114 : 1
m19*m23*0.1
nodelay
--
0
PMID: 11257452 TAK1?TAB2 and MEKK1?ECSIT complexes phosphorylate IKK¦Â.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c119 : 1
stoichiometry:c118 : 1
m86*m35*0.1
nodelay
--
0
PMID: 11257452, 9195953 PKC¦Æ is a downstream target of the LPS-activated PI3K-Akt pathway in human moncytic cells and may be involved in this process. However, the specific site(s) of phosphorylation of p65 was not identified.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c121 : 1
stoichiometry:c122 : 1
stoichiometry:c123 : 1
m89*m31*0.1
nodelay
--
0
PMID: 11257452, 9548485 The N-terminal region (amino acids 1-450) of CBP, a protein highly homologous to p300, specifically interacts with the C-terminal region (amino acids 286-551) of p65 both in vitro and in vivo.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c128 : 1
stoichiometry:c125 : 1
m90*m9*0.1
nodelay
--
0
PMID: 11257452, 7691802, 8521300, 7519214 LPS stimulation of monocytes/macrophages induces the rapid tyrosine phosphorylation of proteins, including the src tyrosine kinase family members p53/56lyn, p58/64c-fgr.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c129 : 1
stoichiometry:c127 : 1
m91*m9*0.1
nodelay
--
0
PMID: 11257452, 7691802, 8521300, 7519214 LPS stimulation of monocytes/macrophages induces the rapid tyrosine phosphorylation of proteins, including the src tyrosine kinase family members p53/56lyn, p58/64c-fgr.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c130 : 1
stoichiometry:c132 : 1
stoichiometry:c131 : 1
m94*m9*0.1
nodelay
--
0
PMID: 11257452, 9195953, 7519214 LPS also activates typical (PKCbeta) and a typical (PKC¦Æ) isoforms of protein kinase C
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c133 : 1
stoichiometry:c135 : 1
stoichiometry:c137 : 1
stoichiometry:c134 : 1
m59*m96*0.1
nodelay
--
0
PMID: 11257452, 7799956, 8513862, 7477354 There is also evidence for LPS activation of the MEK-ERK1/2 pathway via c-Raf-independent pathways. PMID: 11257452, 9820549 Inhibition of MEK in monocytes by U0126 reduced LPS induction of several inflammatory cytokines, including IL-1, IL-8, and TNF¦Á, as well as prostaglandin E2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c146 : 1
stoichiometry:c141 : 1
m100*m51*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1. PMID: 11257452, 8621675 p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1, CHOP, MEF2C, and Sap1a.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c144 : 1
stoichiometry:c148 : 1
stoichiometry:c145 : 1
m101*m51*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1. PMID: 11257452, 9130707 p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1, CHOP, MEF2C, and Sap1a.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c147 : 1
stoichiometry:c143 : 1
m99*m51*0.1
nodelay
--
0
PMID: 11257452 Phosphorylation of Elk-1 in its C-terminal domain induces a conformational change that promotes binding of Elk-1 to Ets sites via its N terminal Ets-domain and to SRF dimers via its B box domain. This results in the assembly of inducible ternary complex consisting of Elk-1 and SRF.Phosphorylation and activation of Elk-1 was inhibited by PD98059, suggesting that Elk-1 is a downstream target of the MEK-ERK1/2 pathway. PMID: 11257452 Many of the downstream targets of the JNK pathway are transcription factors that include c-Jun, ATF-2, and Elk-1. PMID: 11257452 PD98059 inhibited LPS induction of TNF¦Á in human monocytes. PMID: 11257452 PD98059 also inhibits LPS induction of tissue factor gene expression in human moncytes. PMID: 11257452 One of the downstream targets of the MEK-ERK1/2 pathway is the transcription factor Elk-1. PMID: 11257452, 8650547 p38 phosphorylates and activates various transcription factors that include ATF-2, Elk-1, CHOP, MEF2C, and Sap1a.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1
stoichiometry:c25 : 1
m18*m17*m14*0.1
nodelay
--
0
PMID: 11257452 Adaptor protein called TAB2 that mediates activation of TAK1 by linking TAK1 to TRAF6
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS. PMID: 11257452, 78 The N-terminal region (amino acids 1-450) of CBP, a protein highly homologous to p300, specifically interacts with the C-terminal region (amino acids 286-551) of p65 both in vitro and in vivo.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS. PMID: 11257452, 78 The N-terminal region (amino acids 1-450) of CBP, a protein highly homologous to p300, specifically interacts with the C-terminal region (amino acids 286-551) of p65 both in vitro and in vivo.
PMID: 11257452 LPS stimulation of monocytes and macrophages induces many genes that express inflammatory mediators, such as cytokines and chemokines. The transcription factors that bind to these LPS response elements include NF-¦ÊB/Rel proteins, AP-1 proteins, and NF-IL-6. These transcription factors are activated by phosphorylation, which permits the rapid induction of gene expression in response to LPS. PMID: 11257452, 78 The N-terminal region (amino acids 1-450) of CBP, a protein highly homologous to p300, specifically interacts with the C-terminal region (amino acids 286-551) of p65 both in vitro and in vivo.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c152 : 1
stoichiometry:c158 : 1
stoichiometry:c153 : 1
m105*m51*0.1
nodelay
--
0
PMID: 11257452, 9155018 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c159 : 1
stoichiometry:c155 : 1
m106*m51*0.1
nodelay
--
0
PMID: 11257452, 1327754 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c160 : 1
stoichiometry:c157 : 1
m108*m51*0.1
nodelay
--
0
PMID: 11257452, 9628874 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c164 : 1
stoichiometry:c165 : 1
m110*m65*0.1
nodelay
--
0
PMID: 11257452, 10391889 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c162 : 1
stoichiometry:c166 : 1
stoichiometry:c167 : 1
m109*m65*0.1
nodelay
--
0
PMID: 11257452, 10391889 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c161 : 1
stoichiometry:c168 : 1
stoichiometry:c169 : 1
m107*m65*0.1
nodelay
--
0
PMID: 11257452, 10391889 p38 also phosphorylates downstream kinases, including MNK1/2, MAPKAPK2(MK2), MSK1 and PRAK which regulate gene expression by phosphorylating transcription factors such as CREB and ATF-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c172 : 1
stoichiometry:c171 : 1
m9*0.1
nodelay
--
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c14 : 1
m11*m9*0.1
nodelay
--
0
PMID: 11257452 LPS activates the IKK pathway via MyD88, IRAK, and TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c18 : 1
stoichiometry:c17 : 1
m15*m12*0.1
nodelay
--
0
PMID: 11257452 LPS activates the IKK pathway via MyD88, IRAK, and TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c21 : 1
stoichiometry:c20 : 1
m16*m13*0.1
nodelay
--
0
PMID: 11257452 LPS activates the IKK pathway via MyD88, IRAK, and TRAF6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c29 : 1
stoichiometry:c28 : 1
m20*m21*m14*0.1
nodelay
--
0
PMID: 11257452 a novel protein linking TRAF-6 to MEKK1 that was called evolutionarily conserved signaling intermediate in Toll pathways (ECSIT).
cso30:c:OutputProcess
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:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
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:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:OutputProcess
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:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:OutputProcess
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:InputAssociation
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: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:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
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: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:OutputProcess
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:InputAssociation
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
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:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--