J Biol Chem 2001,
PMID: 11136732
Bonacchi, A; Romagnani, P; Romanelli, R G; Efsen, E; Annunziato, F; Lasagni, L; Francalanci, M; Serio, M; Laffi, G; Pinzani, M; Gentilini, P; Marra, F
Hepatic stellate cells (HSC) and glomerular mesangial cells (MC) are tissue-specific pericytes involved in tissue repair, a process that is regulated by members of the chemokine family. In this study, we explored the signal transduction pathways activated by the chemokine receptor CXCR3 in vascular pericytes. In HSC, interaction of CXCR3 with its ligands resulted in increased chemotaxis and activation of the Ras/ERK cascade. Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt. The increase in ERK activity was inhibited by genistein and PP1, but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3. Inhibition of ERK activation resulted in a decreased chemotactic and mitogenic effect of CXCR3 ligands. In MC, which respond to CXCR3 ligands with increased DNA synthesis, CXCR3 activation resulted in a biphasic stimulation of ERK activation, a pattern similar to the one observed in HSC exposed to platelet-derived growth factor, indicating that this type of response is related to the stimulation of cell proliferation. These data characterize CXCR3 signaling in pericytes and clarify the relevance of downstream pathways in the modulation of different biologic responses.
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Text Mining Data
HSC ⊣ CXCR3: "
In
HSC , interaction of
CXCR3 with its ligands
resulted in increased chemotaxis and activation of the Ras/ERK cascade
"
Src → CXCR3: "
Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt
"
Akt → CXCR3: "
Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt
"
ERK ⊣ PP1: "
The increase in ERK activity was inhibited by genistein and PP1 , but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3
"
CXCR3 → Src: "
The increase in ERK activity was inhibited by genistein and PP1, but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3
"
ERK ⊣ CXCR3: "
In MC, which respond to CXCR3 ligands with increased DNA synthesis, CXCR3 activation resulted in a biphasic stimulation of ERK activation, a pattern similar to the one observed in HSC exposed to platelet derived growth factor, indicating that this type of response is related to the stimulation of cell proliferation
"
Manually curated Databases
-
NCI Pathway Database CXCR3-mediated signaling events:
Erk1-2-active (MAPK3/MAPK1)
→
CXCL4/CXCR3-B complex (PF4-CXCR3)
(cell proliferation, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
mTORC2 complex (MTOR-RICTOR-MLST8-MAPKAP1)
→
AKT1 (AKT1)
(modification, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
Erk1-2 (MAPK3/MAPK1)
→
MEK1-2-active (MAP2K1/MAP2K2)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
Erk1-2 (MAPK3/MAPK1)
→
Erk1-2-active (MAPK3/MAPK1)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
MEK1-2-active (MAP2K1/MAP2K2)
→
Erk1-2-active (MAPK3/MAPK1)
(modification, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
None
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
PI3K Class IA family (PIK3CA/PIK3R1/PIK3CB/PIK3R1)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
Erk1-2-active (MAPK3/MAPK1)
→
CXCL9-11/CXCR3-B complex (CXCL10_CXCL11_CXCL9-CXCR3)
(cell proliferation, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
MEK1-2-active (MAP2K1/MAP2K2)
→
MEK1-2 (MAP2K1/MAP2K2)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
MEK1-2 (MAP2K1/MAP2K2)
→
RAF1 (RAF1)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
RAS family/GDP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
Src (SRC)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
RAS family/GTP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
None
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
RAS family/GDP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
→
Src (SRC)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
RAS family/GDP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
→
RAS family/GTP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
RAS family/GDP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
→
None
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
Src (SRC)
→
RAS family/GTP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
(modification, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
Src (SRC)
→
None
(modification, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
RAS family/GTP complex (HRAS_KRAS_HRAS_KRAS_NRAS)
→
None
(modification, collaborate)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
G beta/gamma complex (GNB1-GNG2)
→
PI3K Class IA family (PIK3CA/PIK3R1/PIK3CB/PIK3R1)
(modification, activates)
-
NCI Pathway Database CXCR3-mediated signaling events:
G beta/gamma complex (GNB1-GNG2)
→
Src (SRC)
(modification, activates)
Evidence: assay
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
PDK1 (PDPK1)
(modification, activates)
-
NCI Pathway Database CXCR3-mediated signaling events:
None
→
AKT1 (AKT1)
(modification, activates)
-
NCI Pathway Database CXCR3-mediated signaling events:
PDK1 (PDPK1)
→
AKT1 (AKT1)
(modification, activates)
In total, 55 gene pairs are associated to this article in curated databases