_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e2
_enti_e3
_enti_e55
_enti_e53
_enti_e59
_enti_e52
_enti_e50
_enti_e51
_enti_e56
_enti_e54
_enti_e61
_enti_e57
_enti_e58
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
p1_propro_p1
PMID: 12960231, 10358771
Human immunodeficiency virus type 1 (HIV-1) entry is initiated by binding of the viral envelope (Env) glycoprotein gp120 to CD4 followed by interactions with a G protein-coupled chemokine receptor (GPCR), CCR5 or CXCR4, on the surface of target cells.
PMID: 12960231, 10358771
efficient gp120chemokine interactions typically require that gp120 first binds to CD4 to undergo conformational changes that induce the chemokine receptor binding site.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 12960231, 10358771
Human immunodeficiency virus type 1 (HIV-1) entry is initiated by binding of the viral envelope (Env) glycoprotein gp120 to CD4 followed by interactions with a G protein-coupled chemokine receptor (GPCR), CCR5 or CXCR4, on the surface of target cells.
PMID: 12960231
Here, we will discuss our studies on the intracellular signaling pathways activated in macrophages through CCR5 and CXCR4 in response to envelope proteins from R5 or X4 viruses and contrast them with results in other cell types.
PMID: 12960231, 9120386
The beta-chemokines can block virus entry by competing with gp120 for binding to chemokine receptors.
c8 cso30:c:InputProcess connector
c22 cso30:c:InputProcess connector
c80 cso30:c:InputInhibitor connector
c12 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 12960231, 10358771
Human immunodeficiency virus type 1 (HIV-1) entry is initiated by binding of the viral envelope (Env) glycoprotein gp120 to CD4 followed by interactions with a G protein-coupled chemokine receptor (GPCR), CCR5 or CXCR4, on the surface of target cells.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 12960231, 10358771
Human immunodeficiency virus type 1 (HIV-1) entry is initiated by binding of the viral envelope (Env) glycoprotein gp120 to CD4 followed by interactions with a G protein-coupled chemokine receptor (GPCR), CCR5 or CXCR4, on the surface of target cells.
PMID: 12960231
Here, we will discuss our studies on the intracellular signaling pathways activated in macrophages through CCR5 and CXCR4 in response to envelope proteins from R5 or X4 viruses and contrast them with results in other cell types.
c10 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c11 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 12960231
macrophage-inflammatory protein-1beta (MIP-1beta; CCL4) and stromal derived factor-1alpha (SDF-1alpha; CXCL12), the natural ligands for CCR5 and CXCR4, respectively.
PMIDL 12960231, 10864653
Subsequently, it was reported that HIV-1 and SIV strains with gp120 envelopes that did not elevate [Ca2+]i in macrophages failed to complete replication, and this failure could be complemented by the natural ligand MIP-1, which converted nonproductive infection to productive infection.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c17 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 12960231
macrophage-inflammatory protein-1beta (MIP-1beta; CCL4) and stromal derived factor-1alpha (SDF-1alpha; CXCL12), the natural ligands for CCR5 and CXCR4, respectively.
c15 cso30:c:InputProcess connector
c16 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 12960231
Here, we will discuss our studies on the intracellular signaling pathways activated in macrophages through CCR5 and CXCR4 in response to envelope proteins from R5 or X4 viruses and contrast them with results in other cell types.
PMID: 12960231, 10358771
efficient gp120chemokine interactions typically require that gp120 first binds to CD4 to undergo conformational changes that induce the chemokine receptor binding site.
c7 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 12960231
Here, we will discuss our studies on the intracellular signaling pathways activated in macrophages through CCR5 and CXCR4 in response to envelope proteins from R5 or X4 viruses and contrast them with results in other cell types.
PMID: 12960231, 10358771
efficient gp120chemokine interactions typically require that gp120 first binds to CD4 to undergo conformational changes that induce the chemokine receptor binding site.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c23 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 12960231
CCR5 and CXCR4 elevate [Ca2+]i in a variety of cell types in response to chemokine stimulation.
PMID: 12960231
the peak [Ca2+]i elicited by R5 gp120 was nearly twice that elicited by X4 gp120, with higher steady-state levels as well.
c25 cso30:c:InputAssociation connector
c27 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 12960231
CCR5 and CXCR4 elevate [Ca2+]i in a variety of cell types in response to chemokine stimulation.
PMID: 12960231
the peak [Ca2+]i elicited by R5 gp120 was nearly twice that elicited by X4 gp120, with higher steady-state levels as well.
c26 cso30:c:InputAssociation connector
c28 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 12960231
In some cell types, gp120 is also known to activate the related cytoskeleton-associated focal adhesion kinase (FAK).
c29 cso30:c:InputProcess connector
c31 cso30:c:InputAssociation connector
c30 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 12960231, 7544443
Pyk2 is often Ca2+-regulated.
PMID: 12960231, 10384144, 9362541
Similar results have been reported in T cells, where Pyk2 and FAK are activated by gp120.
c32 cso30:c:InputAssociation connector
c33 cso30:c:InputProcess connector
c34 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 12960231, 9875330
binding of R5 SIV virions (but not gp120 alone) activated JNK and p38 MAPK as well as ERK through CCR5.
PMID: 12960231
Of note, R5 gp120 reliably activated these kinases, and X4 gp120 activation was inconsistent, indicating another difference between the CCR5- and CXCR4-mediated pathways.
c35 cso30:c:InputAssociation connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 12960231, 9875330
binding of R5 SIV virions (but not gp120 alone) activated JNK and p38 MAPK as well as ERK through CCR5.
PMID: 12960231
Of note, R5 gp120 reliably activated these kinases, and X4 gp120 activation was inconsistent, indicating another difference between the CCR5- and CXCR4-mediated pathways.
PMID: 12960231, 11698270
Upon further investigation, we determined that this was dependent on the p38 MAPK pathway, as a specific p38 MAPK inhibitor (SB202190) blocked their secretion.
c36 cso30:c:InputAssociation connector
c41 cso30:c:InputProcess connector
c77 cso30:c:InputInhibitor connector
c42 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 12960231, 9875330
binding of R5 SIV virions (but not gp120 alone) activated JNK and p38 MAPK as well as ERK through CCR5.
PMID: 12960231
Of note, R5 gp120 reliably activated these kinases, and X4 gp120 activation was inconsistent, indicating another difference between the CCR5- and CXCR4-mediated pathways.
c37 cso30:c:InputAssociation connector
c43 cso30:c:InputProcess connector
c44 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 12960231, 9658081
Using CD4+/CXCR4+ cell lines, it was reported that binding of X4 HIV-1 gp120 activated extracellular-regulated kinase (ERK), another member of the MAPK family. However, that response was mediated by CD4, as CD4-independent X4 gp120 did not activate ERK through CXCR4, although the natural CXCR4 ligand SDF-1alpha did.
c38 cso30:c:InputAssociation connector
c45 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 12960231, 9658081
Using CD4+/CXCR4+ cell lines, it was reported that binding of X4 HIV-1 gp120 activated extracellular-regulated kinase (ERK), another member of the MAPK family. However, that response was mediated by CD4, as CD4-independent X4 gp120 did not activate ERK through CXCR4, although the natural CXCR4 ligand SDF-1alpha did.
c47 cso30:c:InputAssociation connector
c48 cso30:c:InputProcess connector
c49 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 12960231, 12551992
Similar results showing that soluble and virion-associated gp120 activates PI-3K in macrophages were recently reported.
c50 cso30:c:InputAssociation connector
c51 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 12960231, 1548758
We also found that HIV gp120 induced macrophage TNF-alpha production.
PMID: 12960231, 2789293, 1918997
It has long been known that gp120 can induce macrophages to secrete tumor necrosis factor alpha (TNF-alpha).
c53 cso30:c:InputAssociation connector
c55 cso30:c:InputAssociation connector
c56 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 12960231, 1548758
We also found that HIV gp120 induced macrophage TNF-alpha production.
c54 cso30:c:InputAssociation connector
c57 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 12960231
Although FAK and ZAP-70 were activated in resting T cells by gp120, it was not clear as to what pathways were specifically responsible for HIV up-regulation.
c58 cso30:c:InputAssociation connector
c59 cso30:c:InputProcess connector
c60 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 12960231
We found that macrophages exposed to gp120 produced MCP-1 and MIP-1beta, consistent with other reports.
PMID: 12960231, 11698270
Upon further investigation, we determined that this was dependent on the p38 MAPK pathway, as a specific p38 MAPK inhibitor (SB202190) blocked their secretion.
c65 cso30:c:InputAssociation connector
c69 cso30:c:InputAssociation connector
c64 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 12960231
We found that macrophages exposed to gp120 produced MCP-1 and MIP-1beta, consistent with other reports.
PMID: 12960231, 11698270
Upon further investigation, we determined that this was dependent on the p38 MAPK pathway, as a specific p38 MAPK inhibitor (SB202190) blocked their secretion.
c67 cso30:c:InputAssociation connector
c63 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 12960231
We found that macrophages exposed to gp120 produced MCP-1 and MIP-1beta, consistent with other reports.
PMID: 12960231, 11698270
Upon further investigation, we determined that this was dependent on the p38 MAPK pathway, as a specific p38 MAPK inhibitor (SB202190) blocked their secretion.
c66 cso30:c:InputAssociation connector
c71 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 12960231
We found that macrophages exposed to gp120 produced MCP-1 and MIP-1beta, consistent with other reports.
PMID: 12960231, 11698270
Upon further investigation, we determined that this was dependent on the p38 MAPK pathway, as a specific p38 MAPK inhibitor (SB202190) blocked their secretion.
c72 cso30:c:InputAssociation connector
c68 cso30:c:InputAssociation connector
c70 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 12960231, 9120386
The beta-chemokines can block virus entry by competing with gp120 for binding to chemokine receptors.
c78 cso30:c:InputProcess connector
c79 cso30:c:InputProcess connector
c81 cso30:c:OutputProcess connector
p22_propro_p22
PMID : 12960231
confirmed pathways(Fig.2.)
c61 cso30:c:InputProcess connector
c73 cso30:c:InputAssociation connector
c62 cso30:c:OutputProcess connector
p22_propro_p27
PMID : 12960231
confirmed pathways(Fig.2.)
c74 cso30:c:InputAssociation connector
c76 cso30:c:InputProcess connector
c82 cso30:c:OutputProcess connector
p22_propro_p28
PMID : 12960231
confirmed pathways(Fig.2.)
c75 cso30:c:InputAssociation connector
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p30_propro_p30
PMID : 12960231
confirmed pathways(Fig.2.)
c85 cso30:c:InputAssociation connector
gp120_enti_MO000036807
gp120
FAK_enti_MO000016855
FAK
CCR5_enti_MO000017281
CCR5
CXCR4_enti_MO000017157
CXCR4
CD4_enti_MO000017819
CD4
gp120: CD4_enti_e5
gp120: CD4
GPCR_enti_MO000000314
GPCR
gp120: CD4: GPCR_enti_e6
gp120: CD4: GPCR
R5 gp120: CD4: CCR5_enti_e11
R5 gp120: CD4: CCR5
X4 gp120: CD4: CXCR4_enti_e12
X4 gp120: CD4: CXCR4
MIP-1beta {extracellular}_enti_MO000019951
MIP-1beta {extracellular}
SDF-1alpha_enti_MO000020121
SDF-1alpha
MIP-1beta: CCR5_enti_e13
MIP-1beta: CCR5
SDF-1alpha: CXCR4_enti_e14
SDF-1alpha: CXCR4
R5 gp120_enti_e15
R5 gp120
X4 gp120_enti_e16
X4 gp120
R5 gp120: CD4_enti_e17
R5 gp120: CD4
X4 gp120: CD4_enti_e18
X4 gp120: CD4
Ca_enti_e19
Ca
FAK {activated}_enti_e20
FAK {activated}
Pyk2_enti_MO000016852
Pyk2
Pyk2{p}_enti_e21
Pyk2{p}
JNK_enti_MO000000023
JNK
JNK {activated}_enti_e22
JNK {activated}
p38_enti_MO000000022
p38
p38 [activated}_enti_e23
p38 [activated}
ERK_enti_MO000000011
ERK
ERK {activated}_enti_e24
ERK {activated}
PI-3K_enti_MO000017257
PI-3K
PI-3K [activated}_enti_e25
PI-3K [activated}
TNF-alpha_enti_G010329
TNF-alpha
TNF-alpha_enti_MO000000289
TNF-alpha
ZAP-70_enti_MO000017772
ZAP-70
ZAP-70 {activated}_enti_e26
ZAP-70 {activated}
MCP-1_enti_MO000017280
MCP-1
MCP1_enti_G010815
MCP1
MIP-1beta_enti_e28
MIP-1beta
MIP-1beta_enti_e29
MIP-1beta
SB202190_enti_e31
SB202190
beta-chemokines_enti_e32
beta-chemokines
beta-chemokines: CCR5_enti_e33
beta-chemokines: CCR5
TFs_enti_e27
TFs
TFs{active}_enti_e30
TFs{active}