Gene interactions and pathways from curated databases and text-mining
J Immunol 2005, PMID: 15728464

CXC chemokine ligand 12-induced focal adhesion kinase activation and segregation into membrane domains is modulated by regulator of G protein signaling 1 in pro-B cells.

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