Original Literature | Model OverView |
---|---|
Publication
Title
Regulation of endogenous apolipoprotein E secretion by macrophages.
Affiliation
Macrophage Biology Group, Centre for Vascular Research, Room 405C Wallace WurthBuilding, University of New South Wales, High Street, Kensington, Sydney, NSW2050, Australia.
Abstract
Apolipoprotein E has critical roles in the protection against atherosclerosisand is understood to follow the classical constitutive secretion pathway. Recentstudies have indicated that the secretion of apoE from macrophages is aregulated process of unexpected complexity. Cholesterol acceptors such asapolipoprotein A-I, high density lipoprotein, and phospholipid vesicles canstimulate apoE secretion. The ATP binding cassette transporter ABCA1 is involvedin basal apoE secretion and in lipidating apoE-containing particles secreted bymacrophages. However, the stimulation of apoE secretion by apoA-I isABCA1-independent, indicating the existence of both ABCA1-dependent and-independent pathways of apoE secretion. The release of apoE under basalconditions is also regulated, requiring intact protein kinase A activity,intracellular calcium, and an intact microtubular network. Mathematical modelingof apoE turnover indicates that whereas some pools of apoE are committed toeither secretion or degradation, other pools can be diverted from degradationtoward secretion. Targeted inhibition or stimulation of specific apoEtrafficking pathways will provide unique opportunities to regulate the biologyof this important molecule.
PMID
18388328
|
Entity
apoE
--
G010197
cso30:c:mRNA
cso30:i:CC_CellComponent
--
csml-variable:Double
m93187
10
infinite
0
TRANSFAC | G010197 |
--
c-Jun {nuclear}
--
MO000000049
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m46
10
infinite
0
InterPro | IPR002112 |
TRANSPATH | MO000000049 |
--
NF-kappaB
--
MO000000058
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m21
10
infinite
0
TRANSPATH | MO000000058 |
--
PLC
--
MO000000132
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m119
10
infinite
0
TRANSPATH | MO000000132 |
--
Lp {extracellular}
--
MO000017793
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m2549
10
infinite
0
TRANSPATH | MO000017793 |
--
IP3R:IP3
--
MO000019288
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3862
10
infinite
0
TRANSPATH | MO000019288 |
--
cytokines
--
MO000019387
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m3957
10
infinite
0
TRANSPATH | MO000019387 |
--
protein remnants
--
MO000019479
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m360980
10
infinite
0
TRANSPATH | MO000019479 |
--
small-molecule hormones
--
MO000021830
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m6165
10
infinite
0
Ensembl | ENSG00000035862 |
TRANSPATH | MO000021830 |
--
oleic acid
--
MO000034006
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m349132
10
infinite
0
TRANSPATH | MO000034006 |
--
LXR:RXR ligand: LXR:RXR
--
MO000056000
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m31324
10
infinite
0
TRANSPATH | MO000056000 |
--
cholesterol
--
MO000056221
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m360460
10
infinite
0
TRANSPATH | MO000056221 |
--
LDL receptor
--
MO000061802
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m36695
10
infinite
0
TRANSPATH | MO000061802 |
--
APOA1
--
MO000062475
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m37363
10
infinite
0
TRANSPATH | MO000062475 |
--
ApoE3 {extracellular}
--
MO000113441
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m355280
10
infinite
0
Affymetrix | 203381_s_at |
Ensembl | ENSG00000130203 |
HGNC | APOE |
OMIM | 104310 |
Proteome | HumanPSD/APOE |
RefSeq | NM_000041 |
TRANSPATH | MO000113441 |
Unigene | Hs.654439 |
UniProt | P02649 |
--
--
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
--
oxysterol
--
e11
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m11
0
infinite
0
--
csml-variable:Double
m12
0
infinite
0
--
csml-variable:Double
m13
0
infinite
0
--
lipid
--
e14
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m14
0
infinite
0
--
PPAR-gamma: apoE-apoC1 intergenic region
--
e15
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m15
0
infinite
0
--
apoE-apoC1 intergenic region
--
e16
cso30:c:Dna
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m16
0
infinite
0
--
c-Jun: AP-1
--
e17
cso30:c:Complex
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m17
0
infinite
0
--
Tpl-2
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m18
0
infinite
0
--
Tpl-2 {activated}
--
e19
cso30:c:Protein
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
--
MEKK1 {activated}
--
e20
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m20
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000000047 |
--
NF-kappaB {activated}
--
e21
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m22
10
infinite
0
TRANSPATH | MO000000058 |
--
c-Jun {activated}
--
e22
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m23
10
infinite
0
InterPro | IPR002112 |
TRANSPATH | MO000000049 |
--
NF-kappaB {nuclear}
--
e24
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m25
10
infinite
0
TRANSPATH | MO000000058 |
--
--
e25
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulum_ExtrinsicToInternalSideOfMembrane_
--
--
--
csml-variable:Double
m26
0
infinite
0
--
--
e26
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulumLumen
--
--
--
csml-variable:Double
m27
0
infinite
0
--
--
e27
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulum_IntegralToMembrane_
--
--
--
csml-variable:Double
m28
0
infinite
0
--
--
e28
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulum_Membrane_
--
--
--
csml-variable:Double
m29
0
infinite
0
--
--
e29
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulum
--
--
--
csml-variable:Double
m30
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
--
e30
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndoplasmicReticulum_ExtrinsicToExternalSideOfMembrane_
--
--
--
csml-variable:Double
m31
0
infinite
0
--
--
e31
cso30:c:EntityBiologicalCompartment
cso30:i:CC_GolgiApparatus
--
--
--
csml-variable:Double
m32
0
infinite
0
--
Apo-E {golgi}
--
e33
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m34
10
infinite
0
TRANSPATH | MO000067564 |
--
--
e34
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Endosome
--
--
--
csml-variable:Double
m35
0
infinite
0
--
--
e35
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeMembrane
--
--
--
csml-variable:Double
m36
0
infinite
0
--
--
e36
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeLumen
--
--
--
csml-variable:Double
m37
0
infinite
0
--
Apo-E {glyT194}{recycling endosomes}
--
e37
cso30:c:Protein
cso30:i:CC_GolgiApparatus
--
csml-variable:Double
m38
0
infinite
0
--
--
e38
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Endosome
--
--
--
csml-variable:Double
m39
0
infinite
0
--
--
e39
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeMembrane
--
--
--
csml-variable:Double
m40
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
--
e40
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeLumen
--
--
--
csml-variable:Double
m41
0
infinite
0
--
Apo-E {early endosome}
--
e41
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m42
10
infinite
0
TRANSPATH | MO000067564 |
--
--
e42
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Lysosome
--
--
--
csml-variable:Double
m43
0
infinite
0
--
--
e43
cso30:c:EntityBiologicalCompartment
cso30:i:CC_LysosomalLumen
--
--
--
csml-variable:Double
m45
0
infinite
0
--
--
e44
cso30:c:EntityBiologicalCompartment
cso30:i:CC_LysosomalMembrane
--
--
--
csml-variable:Double
m47
0
infinite
0
--
Apo-E {lysosome}
--
e45
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m48
10
infinite
0
TRANSPATH | MO000067564 |
--
--
e46
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Endosome
--
--
--
csml-variable:Double
m49
0
infinite
0
--
--
e47
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeMembrane
--
--
--
csml-variable:Double
m63
0
infinite
0
--
--
e48
cso30:c:EntityBiologicalCompartment
cso30:i:CC_EndosomeLumen
--
--
--
csml-variable:Double
m64
0
infinite
0
--
Apo-E {late endosome}
--
e49
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m65
10
infinite
0
TRANSPATH | MO000067564 |
--
Apo-E: LDL receptor
--
e5
cso30:c:Complex
cso30:i:CC_Cytosol
--
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
--
--
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
--
preapoE
--
e63
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m66
0
infinite
0
--
Apo-E{cell surface}
--
e64
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m67
0
infinite
0
--
Apo-E {glyT194}
--
e65
cso30:c:Protein
cso30:i:CC_GolgiApparatus
--
csml-variable:Double
m68
0
infinite
0
--
Apo-E{cell surface}: HSPG2
--
e66
cso30:c:Complex
cso30:i:CC_Extracellular
--
csml-variable:Double
m69
0
infinite
0
--
HDL
--
e67
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
csml-variable:Double
m70
0
infinite
0
--
Apo-E{extracellular}
--
e68
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m71
0
infinite
0
--
Apo-E{extracellular}: HDL
--
e69
cso30:c:Complex
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m72
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
brefeldin A
--
e70
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
csml-variable:Double
m73
0
infinite
0
--
monensin
--
e71
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
csml-variable:Double
m74
0
infinite
0
--
ALLN
--
e72
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m75
0
infinite
0
--
chloroquine
--
e73
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m76
0
infinite
0
--
H89
--
e74
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m77
0
infinite
0
--
heparinase
--
e75
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m78
0
infinite
0
--
ApoE2
--
e77
cso30:c:Protein
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m80
0
infinite
0
--
csml-variable:Double
m81
10
infinite
0
Affymetrix | 203381_s_at |
Ensembl | ENSG00000130203 |
HGNC | APOE |
OMIM | 104310 |
Proteome | HumanPSD/APOE |
RefSeq | NM_000041 |
TRANSPATH | MO000113441 |
Unigene | Hs.654439 |
UniProt | P02649 |
--
csml-variable:Double
m82
10
infinite
0
Affymetrix | 203381_s_at |
Ensembl | ENSG00000130203 |
HGNC | APOE |
OMIM | 104310 |
Proteome | HumanPSD/APOE |
RefSeq | NM_000041 |
TRANSPATH | MO000114092 |
Unigene | Hs.654439 |
UniProt | P02649 |
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
csml-variable:Double
m83
0
infinite
0
--
Ca
--
e81
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m84
0
infinite
0
--
Ca {extracellular}
--
e82
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m85
0
infinite
0
--
csml-variable:Double
m86
10
infinite
0
Affymetrix | 203381_s_at |
Ensembl | ENSG00000130203 |
HGNC | APOE |
OMIM | 104310 |
Proteome | HumanPSD/APOE |
RefSeq | NM_000041 |
TRANSPATH | MO000113441 |
Unigene | Hs.654439 |
UniProt | P02649 |
--
synthetic alpha-hecal peptides
--
e85
cso30:c:SmallMolecule
cso30:i:CC_Extracellular
--
--
csml-variable:Double
m88
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:c2 : 1
stoichiometry:c172 : 1
stoichiometry:c1 : 1
stoichiometry:c3 : 1
m36695*m67*0.1
nodelay
--
0
PMID: 18388328 As a constituent of plasma lipopoproteins, apoE directs movement of lipids from the periphery to the liver, where high affinity binding of apoE to the LDL receptor and other members of the LDL-receptor family facilitates uptake of the lipoprotein particles. PMID: 18388328, 10357834, 9541497 Cell surface apoE can also be bound to lipoprotein receptors, such that antiserum to the LDL receptor (LDLr) and suramin (which blocks ligand binding to the LDL-receptor related protein LRP) can reduce sequestration on the macrophage surface and increase apoE secretion.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c25 : 1
m15*0.1
nodelay
--
0
PMID: 18388328, 11439103 Regulation of apoE transcription by PPARgamma is mediated via a PPRE element present in the intergenic region between the apoE and apoC1 genes, which is also well outside the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.
p11
p11
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1
stoichiometry:c29 : 1
m1746*m219*m46*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c30 : 1
stoichiometry:c31 : 1
m17*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.
p13
p13
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c36 : 1
stoichiometry:c37 : 1
m155666*m18*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
p14
p14
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1
m155666*m44*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c40 : 1
m25*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.
p16
p16
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c44 : 1
stoichiometry:c42 : 1
m21*m20*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
p17
p17
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c43 : 1
stoichiometry:c39 : 1
m21*m19*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c49 : 1
stoichiometry:c48 : 1
m24*m19*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c50 : 1
stoichiometry:c46 : 1
m24*m20*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
p2
p2
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c6 : 1
stoichiometry:c5 : 1
m2549*m5*0.1
nodelay
--
0
PMID: 18388328 As a constituent of plasma lipopoproteins, apoE directs movement of lipids from the periphery to the liver, where high affinity binding of apoE to the LDL receptor and other members of the LDL-receptor family facilitates uptake of the lipoprotein particles.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c52 : 1
m23*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1
m21*0.1
nodelay
--
0
PMID: 18388328, 17553793, 16601234 Other modulators of macrophage apoE transcription have been described, including transforming growth factor (TGF)-beta which stimulates apoE expression by promoting binding of c-Jun to AP-1 and lipopolysaccharide (LPS), which represses apoE gene expression via both Tpl-2 and MEKK1 signaling pathways, leading to c-Jun and NF-kappaB action on distinct regions in the proximal promoter.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1
m93187*0.1
nodelay
--
0
PMID: 18388328 Secretion via tubular and vesicular transport from the Golgi (G), after transport to the Golgi from the endoplasmic reticulum (ER). PMID: 18388328, 6325438 ApoE is synthesized as a 38 500 Mr protein designated preapoE, containing a NH2-terminal 18-AA extension23 which mediates entry into the ER.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c87 : 1
stoichiometry:c59 : 1
m33*0.1
nodelay
--
0
PMID: 18388328 Secretion via tubular and vesicular transport from the Golgi (G), after transport to the Golgi from the endoplasmic reticulum (ER). PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated. PMID: 18388328, 8576639 Brefeldin A, which perturbs ER to Golgi transport, inhibits apoE degradation and causes intracellular accumulation of unglycosylated apoE with lower molecular weight.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1
m68*0.1
nodelay
--
0
PMID: 18388328 Secretion via recycling endosomes (RE). PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE.
p25
p25
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c171 : 1
stoichiometry:c173 : 1
stoichiometry:c74 : 1
m67*m83*0.1
nodelay
--
0
PMID: 18388328 Secretion via recycling endosomes (RE). PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Secretion of apoE (or displacement of cell surface apoE), releases apoE into extracellular medium. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6). PMID: 18388328, 8662812 Increased secretion when proteoglycan synthesis is inhibited suggests that cell surface binding can sequester apoE and inhibit its secretion. PMID: 18388328, 10357834, 9541497 Cell surface apoE can also be bound to lipoprotein receptors, such that antiserum to the LDL receptor (LDLr) and suramin (which blocks ligand binding to the LDL-receptor related protein LRP) can reduce sequestration on the macrophage surface and increase apoE secretion.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c65 : 1
m67*0.1
nodelay
--
0
PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1
m42*0.1
nodelay
--
0
PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
m65*0.1
nodelay
--
0
PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c71 : 1
m48*0.1
nodelay
--
0
PMID: 18388328 Recycling of secreted apoE into early endosomes (EE), and thereafter degraded in lysosomes or proteasomes (Lys/P), transported to Golgi, or secreted via RE. PMID: 18388328, 10671508 Cell surface pools may be reinternalized and subsequently degraded (Figure 1, pathways 3 and 4), or transported to the Golgi network for further modification22 (Figure 1, pathways 3 and 5), or released into the extracellular medium (Figure 1, pathway 3, 2, and 6).
p3
p3
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c10 : 1
m360460*0.1
nodelay
--
0
PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
p30
p30
cso30:i:ME_ProteasomeDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c91 : 1
stoichiometry:c92 : 1
stoichiometry:c88 : 1
stoichiometry:c94 : 1
stoichiometry:c96 : 1
stoichiometry:c73 : 1
m48*0.1
nodelay
--
0
PMID: 18388328 Degradation of apoE in lysosomes or proteasomes (Lys/P), probably via late endosomes (LE). PMID: 18388328, 8576639 Brefeldin A, which perturbs ER to Golgi transport, inhibits apoE degradation and causes intracellular accumulation of unglycosylated apoE with lower molecular weight. PMID: 18388328, 8473293, 9388269 Degradation of apoE is inhibited by ALLN, an inhibitor of Ca2+ dependent proteases, in HepG2 cells, macrophages, and CHO cells expressing apoE. PMID: 18388328, 8576639 Concentrations of the lysosomal inhibitor chloroquine, which effectively inhibited apoE degradation (25 to 100 ?mol/L), did not stimulate apoE secretion. PMID: 18388328, 15066991, 2072040, 1730636 However, as a number of studies have shown that stimulation of apoE secretion by HDL and apoA-I decreases net degradation of apoE, it is likely that there are other "uncommitted" pools of apoE otherwise destined for degradation which can be redirected to secretion. PMID: 18388328, 15066991 ApoA-I stimulates secretion and decreases degradation of Em without affecting Es.
p31
p31
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c89 : 1
stoichiometry:c90 : 1
stoichiometry:c95 : 1
stoichiometry:c97 : 1
stoichiometry:c196 : 1
stoichiometry:c209 : 1
stoichiometry:c64 : 1
m38*m37363*0.1
nodelay
--
0
PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 15066991 ApoA-I stimulates secretion and decreases degradation of Em without affecting Es. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
m34*0.1
nodelay
--
0
PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c77 : 1
m66*0.1
nodelay
--
0
PMID: 18388328, 6286633, 2498325 After cleavage of the signal peptide in the ER, the protein is trafficked to the Golgi, where apoE is O-glycosylated on threonine 194 and extensively sialylated.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c81 : 1
stoichiometry:c82 : 1
m67*m44578*0.1
nodelay
--
0
PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c85 : 1
stoichiometry:c86 : 1
m71*m70*0.1
nodelay
--
0
PMID: 18388328, 15131109 These posttranslational modifications of apoE do not appear to affect receptor binding or lipoprotein clearance but may determine the preferential association with high density lipoprotein (HDL) particles.
p36
p36
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c83 : 1
stoichiometry:c103 : 1
stoichiometry:c105 : 1
stoichiometry:c107 : 1
stoichiometry:c198 : 1
stoichiometry:c211 : 1
stoichiometry:c101 : 1
m38*m349132*0.1
nodelay
--
0
PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 15131109 This is supported by other studies showing that oleic acid stimulates secretion of macrophage apoE while apparently reducing its sialylation. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p37
p37
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c93 : 1
stoichiometry:c102 : 1
stoichiometry:c104 : 1
stoichiometry:c106 : 1
stoichiometry:c197 : 1
stoichiometry:c210 : 1
stoichiometry:c99 : 1
m38*m70*0.1
nodelay
--
0
PMID: 18388328 Poorly glycosylated apoE on cell surface can reenter the Golgi compartment to be further glycosylated, presumably via EE and then LE. PMID: 18388328, 9488694, 8662812 As well as being released into the extracellular medium, a proportion of secreted apoE can be found bound to the cell surface (Figure 1, pathway 7), particularly in association with heparan sulfate proteoglycans. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 15066991, 2072040, 1730636 However, as a number of studies have shown that stimulation of apoE secretion by HDL and apoA-I decreases net degradation of apoE, it is likely that there are other "uncommitted" pools of apoE otherwise destined for degradation which can be redirected to secretion. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328 As H89 is less effective at inhibiting apoA-I?induced apoE secretion than it is at inhibiting constitutive apoE secretion, a second, PKA-independent route of secretion of Em2 is also proposed. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p38
p38
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c119 : 1
stoichiometry:c128 : 1
stoichiometry:c129 : 1
stoichiometry:c130 : 1
stoichiometry:c195 : 1
stoichiometry:c208 : 1
stoichiometry:c109 : 1
m38*m31324*0.1
nodelay
--
0
PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p39
p39
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c120 : 1
stoichiometry:c131 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1
stoichiometry:c194 : 1
stoichiometry:c207 : 1
stoichiometry:c111 : 1
m38*m360460*0.1
nodelay
--
0
PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c11 : 1
m11*0.1
nodelay
--
0
PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
p40
p40
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c121 : 1
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c136 : 1
stoichiometry:c193 : 1
stoichiometry:c206 : 1
stoichiometry:c113 : 1
m38*m3957*0.1
nodelay
--
0
PMID: 18388328, 11149950, 3624230, 1466652 As distinct from factors that increase apoE secretion by stimulating its synthesis (eg, LXR/RXR ligands, cholesterol enrichment, cytokines, a number of agents have been shown to directly increase apoE secretion (independent of transcription). PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p41
p41
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c118 : 1
stoichiometry:c144 : 1
stoichiometry:c150 : 1
stoichiometry:c156 : 1
stoichiometry:c192 : 1
stoichiometry:c205 : 1
stoichiometry:c115 : 1
m38*m290118*0.1
nodelay
--
0
PMID: 18388328, 9388269, 1400506 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p42
p42
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c127 : 1
stoichiometry:c145 : 1
stoichiometry:c151 : 1
stoichiometry:c157 : 1
stoichiometry:c191 : 1
stoichiometry:c204 : 1
stoichiometry:c117 : 1
m38*m40163*0.1
nodelay
--
0
PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p43
p43
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c126 : 1
stoichiometry:c146 : 1
stoichiometry:c152 : 1
stoichiometry:c158 : 1
stoichiometry:c190 : 1
stoichiometry:c203 : 1
stoichiometry:c123 : 1
m38*m43990*0.1
nodelay
--
0
PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p44
p44
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c142 : 1
stoichiometry:c147 : 1
stoichiometry:c153 : 1
stoichiometry:c159 : 1
stoichiometry:c189 : 1
stoichiometry:c202 : 1
stoichiometry:c125 : 1
m38*m79*0.1
nodelay
--
0
PMID: 18388328, 15066991, 17303773, 9869653 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 15066991 Stimulation of apoE secretion is a general property of {alpha}-helix containing molecules including apoA-II, A-IV, and apoE. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p45
p45
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c141 : 1
stoichiometry:c148 : 1
stoichiometry:c154 : 1
stoichiometry:c160 : 1
stoichiometry:c188 : 1
stoichiometry:c201 : 1
stoichiometry:c138 : 1
m38*m78*0.1
nodelay
--
0
PMID: 18388328, 9488694, 8662812, 10671508 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p46
p46
cso30:i:ME_Translocation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c143 : 1
stoichiometry:c149 : 1
stoichiometry:c155 : 1
stoichiometry:c161 : 1
stoichiometry:c187 : 1
stoichiometry:c200 : 1
stoichiometry:c140 : 1
m38*m41742*0.1
nodelay
--
0
PMID: 18388328, 9488694, 8662812, 10671508 These include, LDL,HDL,apoA-I, A-II, A-IV, apoE,phospholipid vesicles (PLV), heparinase, oleic acid, and lactoferrin. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p47
p47
cso30:i:ME_Translocation
cso30:i:CC_Extracellular
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c162 : 1
stoichiometry:c165 : 1
stoichiometry:c163 : 1
m81*m86*0.1
nodelay
--
0
PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.
p48
p48
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c164 : 1
stoichiometry:c167 : 1
stoichiometry:c166 : 1
m81*m80*0.1
nodelay
--
0
PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.
p49
p49
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c168 : 1
stoichiometry:c170 : 1
stoichiometry:c169 : 1
m81*m82*0.1
nodelay
--
0
PMID: 18388328, 15066991, 10441097 Exogenous apoE4 is less effective at stimulating apoE3 secretion from macrophages than are apoE3 and apoE2, which may be relevant for the increased atherosclerotic risk associated with the apoE4 phenotype.
p5
p5
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c12 : 1
m3957*0.1
nodelay
--
0
PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
p50
p50
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c174 : 1
stoichiometry:c176 : 1
stoichiometry:c175 : 1
m84*m67*0.1
nodelay
--
0
PMID: 18388328, 15066991, 6823554 Although the pathways stimulating apoE secretion and cholesterol efflux are distinct, apoE, whether added to cells or during its secretion from cells, can itself mediate cholesterol efflux.
p51
p51
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c177 : 1
stoichiometry:c179 : 1
stoichiometry:c180 : 1
stoichiometry:c178 : 1
m84*m87*m63632*0.1
nodelay
--
0
PMID: 18388328, 16254198 There is evidence to suggest that exogenous apoE removes cholesterol via an ABCA1-mediated pathway, whereas secreted apoE may also remove cholesterol in an ABCA1-independent manner.
p52
p52
cso30:i:ME_Translocation
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c181 : 1
stoichiometry:c183 : 1
stoichiometry:c184 : 1
stoichiometry:c185 : 1
stoichiometry:c186 : 1
stoichiometry:c199 : 1
stoichiometry:c212 : 1
stoichiometry:c182 : 1
m38*m88*0.1
nodelay
--
0
PMID: 18388328, 15066991 Additionally, a range of synthetic alpha-helical peptides which stimulated apoE secretion to an extent similar to intact apoA-I were incapable of stimulating cholesterol efflux. PMID: 18388328, 8576639, 6823554 Monensin and brefeldin A inhibit endogenous apoE secretion, but fail to affect recycling of I-apoE-VLDL delivered to CHO cells, supporting the existence of different secretory pathways for endogenous and recycled apoE. PMID: 18388328, 17660382 The PKA inhibitor H89 inhibits secretion of apoE without increasing degradation and increases the stable pool Es. PMID: 18388328, 17660382 As inhibitors of phospholipase C (PLC) and the inositol triphosphate (IP3) receptor (IP3R) also decreased secretion of apoE, a role for PLC and IP3R in the mobilization of [Ca2+]i during secretion of apoE is most likely.
p6
p6
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
m6165*0.1
nodelay
--
0
PMID: 18388328 Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c20 : 1
stoichiometry:c19 : 1
m13*m14*0.1
nodelay
--
0
PMID: 18388328 The LXR/RXR heterodimer regulates apoE transcription in response to lipids through interaction with conserved LXR response elements in the multienhancer regions. PMID: 18388328, 17553793, 16601234, 11149950, 11439103 Transcription factors involved in the direct transcriptional regulation of apoE in macrophages included: AP-1, NF-kappaB LXR and PPARgamma.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1
m31324*m12*0.1
nodelay
--
0
PMID: 18388328 The LXR/RXR heterodimer regulates apoE transcription in response to lipids through interaction with conserved LXR response elements in the multienhancer regions.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c24 : 1
stoichiometry:c22 : 1
m357146*m16*0.1
nodelay
--
0
PMID: 18388328, 11439103 Regulation of apoE transcription by PPARgamma is mediated via a PPRE element present in the intergenic region between the apoE and apoC1 genes, which is also well outside the proximal promoter.
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
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0
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--
cso30:c:InputInhibitor
threshold
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cso30:c:InputInhibitor
threshold
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cso30:c:InputInhibitor
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cso30:c:InputInhibitor
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cso30:c:InputProcess
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cso30:c:InputProcess
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cso30:c:OutputProcess
threshold
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cso30:c:InputProcess
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputProcess
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputProcess
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:InputProcess
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputProcess
threshold
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cso30:c:OutputProcess
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:InputAssociation
threshold
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cso30:c:InputInhibitor
threshold
--
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
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cso30:c:InputInhibitor
threshold
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cso30:c:InputInhibitor
threshold
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0
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cso30:c:InputInhibitor
threshold
--
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cso30:c:InputInhibitor
threshold
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0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputProcess
threshold
--
0
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cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputInhibitor
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: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:OutputProcess
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:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
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--
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:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputProcess
threshold
--
0
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--
cso30:c:OutputProcess
threshold
--
0
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--
cso30:c:InputAssociation
threshold
--
0
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--
cso30:c:OutputProcess
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:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--