J Immunol 2005,
PMID: 15728464
Le, Yi; Honczarenko, Marek; Glodek, Aleksandra M; Ho, Daniel K; Silberstein, Leslie E
CXCL12-induced chemotaxis and adhesion to VCAM-1 decrease as B cells differentiate in the bone marrow. However, the mechanisms that regulate CXCL12/CXCR4-mediated signaling are poorly understood. We report that after CXCL12 stimulation of progenitor B cells, focal adhesion kinase (FAK) and PI3K are inducibly recruited to raft-associated membrane domains. After CXCL12 stimulation, phosphorylated FAK is also localized in membrane domains. The CXCL12/CXCR4-FAK pathway is membrane cholesterol dependent and impaired by metabolic inhibitors of G(i), Src family, and the GTPase-activating protein, regulator of G protein signaling 1 (RGS1). In the bone marrow, RGS1 mRNA expression is low in progenitor B cells and high in mature B cells, implying developmental regulation of CXCL12/CXCR4 signaling by RGS1. CXCL12-induced chemotaxis and adhesion are impaired when FAK recruitment and phosphorylation are inhibited by either membrane cholesterol depletion or overexpression of RGS1 in progenitor B cells. We conclude that the recruitment of signaling molecules to specific membrane domains plays an important role in CXCL12/CXCR4-induced cellular responses.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed
Text Mining Data
CXCL12/CXCR4 — RGS1: "
In the bone marrow, RGS1 mRNA expression is low in progenitor B cells and high in mature B cells, implying developmental
regulation of
CXCL12/CXCR4 signaling by
RGS1
"
CXCL12/CXCR4 — RGS1: "
In the bone marrow, RGS1 mRNA expression is low in progenitor B cells and high in mature B cells, implying developmental regulation of CXCL12/CXCR4 signaling by RGS1
"
Manually curated Databases
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK/p130 Cas/Paxillin complex (PTK2-BCAR1-PXN)
→
FAK (PTK2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK/p130 Cas/Paxillin complex (PTK2-BCAR1-PXN)
→
p130 Cas (BCAR1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK/p130 Cas/Paxillin complex (PTK2-BCAR1-PXN)
→
Paxillin (PXN)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
FAK (PTK2)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
p130 Cas (BCAR1)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
G beta/gamma complex (GNB1-GNG2)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
SDF1/CXCR4/JAK2 complex (CXCL12-CXCR4-JAK2)
→
Paxillin (PXN)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
→
FAK (PTK2)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
→
p130 Cas (BCAR1)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
→
G beta/gamma complex (GNB1-GNG2)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Src Family Kinases-active (FGR/LYN/LCK/YES1/BLK/HCK/SRC/FYN)
→
Paxillin (PXN)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK (PTK2)
→
p130 Cas (BCAR1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK (PTK2)
→
G beta/gamma complex (GNB1-GNG2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK (PTK2)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
FAK (PTK2)
→
Paxillin (PXN)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
p130 Cas (BCAR1)
→
G beta/gamma complex (GNB1-GNG2)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
p130 Cas (BCAR1)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
p130 Cas (BCAR1)
→
Paxillin (PXN)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
G beta/gamma complex (GNB1-GNG2)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
G beta/gamma complex (GNB1-GNG2)
→
Paxillin (PXN)
(modification, activates)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
→
Paxillin (PXN)
(modification, inhibits)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database CXCR4-mediated signaling events:
G beta/gamma complex (GNB1-GNG2)
→
Gi family/GTP/RGS1 complex (GNAI2_GNAI3_GNAO1_GNAO1_GNAZ_GNAI1-RGS1)
(modification, activates)
Evidence: mutant phenotype, assay
In total, 196 gene pairs are associated to this article in curated databases