_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e3
_enti_e4
_enti_e2
_enti_e31
_enti_e46
_enti_e55
_enti_e42
_enti_e38
_enti_e34
_enti_e29
_enti_e48
_enti_e47
_enti_e59
_enti_e53
_enti_e43
_enti_e44
_enti_e39
_enti_e40
_enti_e35
_enti_e36
_enti_e28
_enti_e26
_enti_e50
_enti_e51
_enti_e54
_enti_e56
_enti_e52
_enti_e30
_enti_e25
_enti_e27
_enti_e61
_enti_e57
_enti_e58
_enti_e60
_enti_e62
g1_fact_g7
g2_fact_g2
g2_fact_g12
g2_fact_g13
g1_fact_g1
g1_fact_g14
g1_fact_g6
g1_fact_g5
g1_fact_g4
g1_fact_g3
p1_propro_p1
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.
c2 cso30:c:InputProcess connector
c172 cso30:c:InputInhibitor connector
c1 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
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.
c4 cso30:c:InputProcess connector
c6 cso30:c:InputAssociation connector
c5 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18388328
Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
c7 cso30:c:InputAssociation connector
c10 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 18388328
Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
c8 cso30:c:InputAssociation connector
c11 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 18388328
Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
c9 cso30:c:InputAssociation connector
c12 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 18388328
Transcription of macrophage apoE can be induced by differentiation, exposure to cytokines, hormones, and lipids such as cholesterol or oxysterols.
c13 cso30:c:InputAssociation connector
c14 cso30:c:OutputProcess connector
p7_propro_p7
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.
c18 cso30:c:InputAssociation connector
c20 cso30:c:InputAssociation connector
c19 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 18388328
The LXR/RXR heterodimer regulates apoE transcription in response to lipids through interaction with conserved LXR response elements in the multienhancer regions.
c15 cso30:c:InputProcess connector
c16 cso30:c:InputProcess connector
c17 cso30:c:OutputProcess connector
p9_propro_p9
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.
c21 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c22 cso30:c:OutputProcess connector
p10_propro_p10
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.
c23 cso30:c:InputAssociation connector
c25 cso30:c:OutputProcess connector
p11_propro_p11
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.
c26 cso30:c:InputAssociation connector
c27 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p12_propro_p12
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.
c30 cso30:c:InputAssociation connector
c31 cso30:c:OutputProcess connector
p13_propro_p13
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.
c32 cso30:c:InputAssociation connector
c36 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p14_propro_p14
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.
c33 cso30:c:InputAssociation connector
c34 cso30:c:InputProcess connector
c35 cso30:c:OutputProcess connector
p15_propro_p15
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.
c55 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p16_propro_p16
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.
c41 cso30:c:InputProcess connector
c44 cso30:c:InputAssociation connector
c42 cso30:c:OutputProcess connector
p17_propro_p17
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.
c38 cso30:c:InputProcess connector
c43 cso30:c:InputAssociation connector
c39 cso30:c:OutputProcess connector
p18_propro_p18
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.
c47 cso30:c:InputProcess connector
c49 cso30:c:InputAssociation connector
c48 cso30:c:OutputProcess connector
p19_propro_p19
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.
c45 cso30:c:InputProcess connector
c50 cso30:c:InputAssociation connector
c46 cso30:c:OutputProcess connector
p20_propro_p20
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.
c51 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p21_propro_p21
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.
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p22_propro_p22
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.
c56 cso30:c:InputAssociation connector
c57 cso30:c:OutputProcess connector
p23_propro_p23
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.
c58 cso30:c:InputProcess connector
c87 cso30:c:InputInhibitor connector
c59 cso30:c:OutputProcess connector
p24_propro_p24
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.
c60 cso30:c:InputProcess connector
c61 cso30:c:OutputProcess connector
p25_propro_p25
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.
c63 cso30:c:InputProcess connector
c171 cso30:c:InputInhibitor connector
c173 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p26_propro_p26
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).
c75 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
p27_propro_p27
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.
c66 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p28_propro_p28
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.
c68 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p29_propro_p29
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).
c70 cso30:c:InputProcess connector
c71 cso30:c:OutputProcess connector
p30_propro_p30
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.
c72 cso30:c:InputProcess connector
c91 cso30:c:InputInhibitor connector
c92 cso30:c:InputInhibitor connector
c88 cso30:c:InputInhibitor connector
c94 cso30:c:InputInhibitor connector
c96 cso30:c:InputInhibitor connector
c73 cso30:c:OutputProcess connector
p31_propro_p31
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-Iinduced 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.
c62 cso30:c:InputProcess connector
c89 cso30:c:InputInhibitor connector
c90 cso30:c:InputInhibitor connector
c95 cso30:c:InputAssociation connector
c97 cso30:c:InputInhibitor connector
c196 cso30:c:InputInhibitor connector
c209 cso30:c:InputInhibitor connector
c64 cso30:c:OutputProcess connector
p33_propro_p33
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.
c76 cso30:c:InputProcess connector
c77 cso30:c:OutputProcess connector
p32_propro_p32
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.
c78 cso30:c:InputProcess connector
c79 cso30:c:OutputProcess connector
p34_propro_p34
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.
c80 cso30:c:InputProcess connector
c81 cso30:c:InputProcess connector
c82 cso30:c:OutputProcess connector
p35_propro_p35
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.
c84 cso30:c:InputProcess connector
c85 cso30:c:InputProcess connector
c86 cso30:c:OutputProcess connector
p36_propro_p36
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-Iinduced 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.
c100 cso30:c:InputProcess connector
c83 cso30:c:InputAssociation connector
c103 cso30:c:InputInhibitor connector
c105 cso30:c:InputInhibitor connector
c107 cso30:c:InputInhibitor connector
c198 cso30:c:InputInhibitor connector
c211 cso30:c:InputInhibitor connector
c101 cso30:c:OutputProcess connector
p37_propro_p37
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-Iinduced 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.
c98 cso30:c:InputProcess connector
c93 cso30:c:InputAssociation connector
c102 cso30:c:InputInhibitor connector
c104 cso30:c:InputInhibitor connector
c106 cso30:c:InputInhibitor connector
c197 cso30:c:InputInhibitor connector
c210 cso30:c:InputInhibitor connector
c99 cso30:c:OutputProcess connector
p38_propro_p38
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.
c108 cso30:c:InputProcess connector
c119 cso30:c:InputAssociation connector
c128 cso30:c:InputInhibitor connector
c129 cso30:c:InputInhibitor connector
c130 cso30:c:InputInhibitor connector
c195 cso30:c:InputInhibitor connector
c208 cso30:c:InputInhibitor connector
c109 cso30:c:OutputProcess connector
p39_propro_p39
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.
c110 cso30:c:InputProcess connector
c120 cso30:c:InputAssociation connector
c131 cso30:c:InputInhibitor connector
c132 cso30:c:InputInhibitor connector
c133 cso30:c:InputInhibitor connector
c194 cso30:c:InputInhibitor connector
c207 cso30:c:InputInhibitor connector
c111 cso30:c:OutputProcess connector
p40_propro_p40
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.
c112 cso30:c:InputProcess connector
c121 cso30:c:InputAssociation connector
c134 cso30:c:InputInhibitor connector
c135 cso30:c:InputInhibitor connector
c136 cso30:c:InputInhibitor connector
c193 cso30:c:InputInhibitor connector
c206 cso30:c:InputInhibitor connector
c113 cso30:c:OutputProcess connector
p41_propro_p41
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.
c114 cso30:c:InputProcess connector
c118 cso30:c:InputAssociation connector
c144 cso30:c:InputInhibitor connector
c150 cso30:c:InputInhibitor connector
c156 cso30:c:InputInhibitor connector
c192 cso30:c:InputInhibitor connector
c205 cso30:c:InputInhibitor connector
c115 cso30:c:OutputProcess connector
p42_propro_p42
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.
c116 cso30:c:InputProcess connector
c127 cso30:c:InputAssociation connector
c145 cso30:c:InputInhibitor connector
c151 cso30:c:InputInhibitor connector
c157 cso30:c:InputInhibitor connector
c191 cso30:c:InputInhibitor connector
c204 cso30:c:InputInhibitor connector
c117 cso30:c:OutputProcess connector
p43_propro_p43
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.
c122 cso30:c:InputProcess connector
c126 cso30:c:InputAssociation connector
c146 cso30:c:InputInhibitor connector
c152 cso30:c:InputInhibitor connector
c158 cso30:c:InputInhibitor connector
c190 cso30:c:InputInhibitor connector
c203 cso30:c:InputInhibitor connector
c123 cso30:c:OutputProcess connector
p44_propro_p44
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.
c124 cso30:c:InputProcess connector
c142 cso30:c:InputAssociation connector
c147 cso30:c:InputInhibitor connector
c153 cso30:c:InputInhibitor connector
c159 cso30:c:InputInhibitor connector
c189 cso30:c:InputInhibitor connector
c202 cso30:c:InputInhibitor connector
c125 cso30:c:OutputProcess connector
p45_propro_p45
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.
c137 cso30:c:InputProcess connector
c141 cso30:c:InputAssociation connector
c148 cso30:c:InputInhibitor connector
c154 cso30:c:InputInhibitor connector
c160 cso30:c:InputInhibitor connector
c188 cso30:c:InputInhibitor connector
c201 cso30:c:InputInhibitor connector
c138 cso30:c:OutputProcess connector
p46_propro_p46
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.
c139 cso30:c:InputProcess connector
c143 cso30:c:InputAssociation connector
c149 cso30:c:InputInhibitor connector
c155 cso30:c:InputInhibitor connector
c161 cso30:c:InputInhibitor connector
c187 cso30:c:InputInhibitor connector
c200 cso30:c:InputInhibitor connector
c140 cso30:c:OutputProcess connector
p47_propro_p47
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.
c162 cso30:c:InputProcess connector
c165 cso30:c:InputAssociation connector
c163 cso30:c:OutputProcess connector
p48_propro_p48
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.
c164 cso30:c:InputProcess connector
c167 cso30:c:InputAssociation connector
c166 cso30:c:OutputProcess connector
p49_propro_p49
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.
c168 cso30:c:InputProcess connector
c170 cso30:c:InputAssociation connector
c169 cso30:c:OutputProcess connector
p50_propro_p50
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.
c174 cso30:c:InputProcess connector
c176 cso30:c:InputAssociation connector
c175 cso30:c:OutputProcess connector
p51_propro_p51
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.
c177 cso30:c:InputProcess connector
c179 cso30:c:InputAssociation connector
c180 cso30:c:InputAssociation connector
c178 cso30:c:OutputProcess connector
p52_propro_p52
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.
c181 cso30:c:InputProcess connector
c183 cso30:c:InputInhibitor connector
c184 cso30:c:InputInhibitor connector
c185 cso30:c:InputInhibitor connector
c186 cso30:c:InputAssociation connector
c199 cso30:c:InputInhibitor connector
c212 cso30:c:InputInhibitor connector
c182 cso30:c:OutputProcess connector
LDL_enti_MO000000290
LDL
LDL receptor_enti_MO000061802
LDL receptor
Lp {extracellular}_enti_MO000017793
Lp {extracellular}
Apo-E: LDL receptor_enti_e5
Apo-E: LDL receptor
Lp_enti_e6
Lp
apoE_enti_G010197
apoE
cytokines_enti_MO000019387
cytokines
cholesterol_enti_MO000056221
cholesterol
oxysterol_enti_e11
oxysterol
small-molecule hormones_enti_MO000021830
small-molecule hormones
LXR:RXR ligand: LXR:RXR_enti_MO000056000
LXR:RXR ligand: LXR:RXR
apo-E_enti_e12
apo-E
apo-E: LXR:RXR_enti_e13
apo-E: LXR:RXR
lipid_enti_e14
lipid
PPAR-gamma_enti_MO000047193
PPAR-gamma
PPAR-gamma: apoE-apoC1 intergenic region_enti_e15
PPAR-gamma: apoE-apoC1 intergenic region
apoE-apoC1 intergenic region_enti_e16
apoE-apoC1 intergenic region
TGFbeta_enti_MO000016808
TGFbeta
c-Jun {nuclear}_enti_MO000000049
c-Jun {nuclear}
AP-1_enti_MO000000276
AP-1
c-Jun: AP-1_enti_e17
c-Jun: AP-1
Tpl-2_enti_e18
Tpl-2
MEKK1_enti_MO000000047
MEKK1
LPS_enti_MO000016882
LPS
Tpl-2 {activated}_enti_e19
Tpl-2 {activated}
MEKK1 {activated}_enti_e20
MEKK1 {activated}
NF-kappaB_enti_MO000000058
NF-kappaB
NF-kappaB {activated}_enti_e21
NF-kappaB {activated}
c-Jun {activated}_enti_e22
c-Jun {activated}
c-Jun_enti_e23
c-Jun
NF-kappaB {nuclear}_enti_e24
NF-kappaB {nuclear}
Apo-E {ER}_enti_e32
Apo-E {ER}
Apo-E {golgi}_enti_e33
Apo-E {golgi}
Apo-E {early endosome}_enti_e41
Apo-E {early endosome}
Apo-E {lysosome}_enti_e45
Apo-E {lysosome}
Apo-E {late endosome}_enti_e49
Apo-E {late endosome}
protein remnants_enti_MO000019479
protein remnants
Apo-E{cell surface}_enti_e64
Apo-E{cell surface}
preapoE_enti_e63
preapoE
Apo-E {glyT194}_enti_e65
Apo-E {glyT194}
Apo-E {glyT194}{recycling endosomes}_enti_e37
Apo-E {glyT194}{recycling endosomes}
HSPG2_enti_MO000069735
HSPG2
Apo-E{cell surface}: HSPG2_enti_e66
Apo-E{cell surface}: HSPG2
oleic acid_enti_MO000034006
oleic acid
HDL_enti_e67
HDL
Apo-E{extracellular}_enti_e68
Apo-E{extracellular}
Apo-E{extracellular}: HDL_enti_e69
Apo-E{extracellular}: HDL
brefeldin A_enti_e70
brefeldin A
monensin_enti_e71
monensin
ALLN_enti_e72
ALLN
chloroquine_enti_e73
chloroquine
APOA1_enti_MO000062475
APOA1
H89_enti_e74
H89
APOA2_enti_MO000065296
APOA2
APOA4_enti_MO000069146
APOA4
heparinase_enti_e75
heparinase
Apo-E_enti_e76
Apo-E
LTF_enti_MO000066885
LTF
ApoE3 {extracellular}_enti_MO000113441
ApoE3 {extracellular}
ApoE2_enti_e77
ApoE2
ApoE3_enti_e78
ApoE3
ApoE4_enti_e79
ApoE4
suramin_enti_e80
suramin
ABCA1_enti_MO000090073
ABCA1
Ca_enti_e81
Ca
Ca {extracellular}_enti_e82
Ca {extracellular}
ApoE3 {exogenous}_enti_e83
ApoE3 {exogenous}
Apo-E {exogenous}_enti_e84
Apo-E {exogenous}
synthetic alpha-hecal peptides_enti_e85
synthetic alpha-hecal peptides
IP3R:IP3_enti_MO000019288
IP3R:IP3
PLC_enti_MO000000132
PLC