Blood 2003,
PMID: 12750173
Smit, Martine J; Verdijk, Pauline; van der Raaij-Helmer, Elisabeth M H; Navis, Marjon; Hensbergen, Paul J; Leurs, Rob; Tensen, Cornelis P
The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells. These interferon gamma (IFNgamma)-induced chemokines are thought to be crucial in directing activated T cells to sites of inflammation. As such, they play an important role in several chronic inflammatory diseases including ulcerative colitis, multiple sclerosis, artherosclerosis, and delayed-type hypersensitivity reactions of the skin. In this study, we first demonstrate that in COS-7 cells heterologously expressing CXCR3, CXCL11 is a potent activator of the pertussis toxin (PTX)-sensitive p44/p42 mitogen-activated protein kinase (MAPK) and Akt/phosphatidylinositol 3 kinase (PI3K) pathways. Next, we show that these signal transduction pathways are also operative and PTX sensitive in primary human T cells expressing CXCR3. Importantly, abrogation of these signaling cascades by specific inhibitors did not block the migration of T cells toward CXCR3 ligands, suggesting that MAPK and Akt activation is not crucial for CXCR3-mediated chemotaxis of T cells. Finally, we demonstrate that CXCR3-targeting chemokines control T-cell migration via PTX-sensitive, phospholipase C pathways and phosphatidylinositol kinases other than class I PI3Kgamma.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed
Text Mining Data
Dashed line = No text mining data
Manually curated Databases
-
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:
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:
G beta/gamma complex (GNB1-GNG2)
→
PI3K Class IA family (PIK3CA/PIK3R1/PIK3CB/PIK3R1)
(modification, activates)
-
NCI Pathway Database CXCR3-mediated signaling events:
GNAI3/GDP complex (GNAI3)
→
GNAI2/GTP complex (GNAI2)
(chemotaxis, inhibits)
Evidence: mutant phenotype, 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, 31 gene pairs are associated to this article in curated databases