Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1994, PMID: 7528218

Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors.

Weng, W K; Jarvis, L; LeBien, T W

The B cell-specific cell surface molecule CD19 plays a role in regulating immunoglobulin (Ig) receptor signaling, and cross-linking CD19 activates several signaling molecules in mature human B cells. In surface Ig-negative B cell precursors, a protein tyrosine kinase (PTK)-dependent homotypic aggregation response can be triggered by cross-linking CD19. In the current study, we examined the outcome of PTK-mediated signal transduction following CD19 cross-linking on surface Ig negative and surface Ig positive B cell lines, as well as freshly isolated surface Ig-negative B cell precursors. PTK activation resulted in the tyrosine phosphorylation of multiple protein substrates and peaked at 0.5-1 min following CD19 cross-linking in all B-lineage cells examined. One of the tyrosine-phosphorylated substrates was identified as the hematopoietic-specific protein Vav, a guanine nucleotide exchange factor that activates the Ras pathway. Evidence consistent with Ras pathway activation was also demonstrated by MEK activation and subsequent phosphorylation of a MAP kinase fusion protein. CD19 cross-linking, sequential immunoprecipitation, and Western blotting revealed that: (a) Vav becomes associated with CD19, (b) phosphatidylinositol 3-kinase (PI 3-kinase) becomes associated with CD19, and (c) PI 3-kinase becomes associated with Vav. No such physical interaction occurred following control IgG1 cross-linking or cross-linking of class I major histocompatability complex cell surface molecules. Coupled with a previous report (Tuveson, D.A., Carter, R.H., Soltoff, S.P., and Fearon, D.T. (1993) Science 260, 986-988), our data support a model in which CD19 cross-linking induces the formation of a signaling complex that leads to the activation of two pathways involving Ras and PI 3-kinase.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: CD19 — VAV1 (physical association, affinity chromatography technology)
  • MIPS CORUM CD19-Vav-PI 3-kinase (p85 subunit) complex: CD19-Vav-PI 3-kinase (p85 subunit) complex complex (CD19-PIK3R1-VAV1)
  • IRef Hprd Interaction: CD19 — PIK3R1 (in vivo)
  • IRef Hprd Interaction: Complex of 22 proteins (in vivo)
  • IRef Hprd Interaction: CD19 — VAV1 (in vivo)
  • IRef Ophid Interaction: CD19 — PIK3R1 (aggregation, confirmational text mining)
  • NCI Pathway Database BCR signaling pathway: CD19 (CD19) → B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: CD19 (CD19) → PI3K/BCAP/CD19 complex (CD19-PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: CD19 (CD19) → VAV2 (VAV2) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: CD19 (CD19) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) → PI3K/BCAP/CD19 complex (CD19-PIK3CA-PIK3R1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) → VAV2 (VAV2) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) → PI3K complex (PIK3CA-PIK3R1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: PI3K/BCAP/CD19 complex (CD19-PIK3CA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BCR signaling pathway: VAV2 (VAV2) → PI3K complex (PIK3CA-PIK3R1) (modification, activates)
    Evidence: assay, physical interaction
  • Reactome Reaction: CD79B → NCK1 (indirect_complex)
  • Reactome Reaction: SYK → SHC1 (indirect_complex)
  • Reactome Reaction: IGHM → DAPP1 (indirect_complex)
  • Reactome Reaction: NCK1 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → DAPP1 (indirect_complex)
  • Reactome Reaction: NCK1 → CBLB (indirect_complex)
  • Reactome Reaction: CD79B → DAPP1 (indirect_complex)
  • Reactome Reaction: PLCG2 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: PIK3CD → PIK3AP1 (indirect_complex)
  • Reactome Reaction: BTK → IGHM (indirect_complex)
  • Reactome Reaction: IGKV4-1 → VAV1 (indirect_complex)
  • Reactome Reaction: PLCG1 → BLNK (indirect_complex)
  • Reactome Reaction: IGKV1-5 → DAPP1 (indirect_complex)
  • Reactome Reaction: IGHM → PLCG1 (indirect_complex)
  • Reactome Reaction: BTK → IGKV1-5 (indirect_complex)
  • Reactome Reaction: PIK3CD → VAV1 (indirect_complex)
  • Reactome Reaction: PIK3R1 → VAV1 (indirect_complex)
  • Reactome Reaction: PLCG2 → BLNK (indirect_complex)
  • Reactome Reaction: SOS1 → VAV1 (indirect_complex)
  • Reactome Reaction: VAV1 → IGLC3 (indirect_complex)
  • Reactome Reaction: SYK → DAPP1 (indirect_complex)
  • Reactome Reaction: NCK1 → SHC1 (direct_complex)
  • Reactome Reaction: GRB2 → DAPP1 (indirect_complex)
  • Reactome Reaction: SYK → NCK1 (indirect_complex)
  • Reactome Reaction: BTK → SYK (indirect_complex)
  • Reactome Reaction: CD79A → SHC1 (indirect_complex)
  • Reactome Reaction: DAPP1 → IGLC6 (indirect_complex)
  • Reactome Reaction: NCK1 → PLCG2 (indirect_complex)
  • Reactome Reaction: PIK3R1 → PIK3AP1 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC6 (indirect_complex)
  • Reactome Reaction: VAV1 → IGLC7 (indirect_complex)
  • Reactome Reaction: BTK → IGKV4-1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PLCG2 (indirect_complex)
  • Reactome Reaction: CD79A → PLCG2 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC3 (indirect_complex)
  • Reactome Reaction: PLCG2 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGHD → VAV1 (indirect_complex)
  • Reactome Reaction: DAPP1 → SHC1 (indirect_complex)
  • Reactome Reaction: SYK → VAV1 (indirect_complex)
  • Reactome Reaction: SHC1 → BLNK (indirect_complex)
  • Reactome Reaction: CD79B → VAV1 (indirect_complex)
  • Reactome Reaction: DAPP1 → IGLC3 (indirect_complex)
  • Reactome Reaction: BTK → IGLC1 (indirect_complex)
  • Reactome Reaction: IGKC → PLCG1 (indirect_complex)
  • Reactome Reaction: PLCG2 → SHC1 (indirect_complex)
  • Reactome Reaction: BTK → IGKC (indirect_complex)
  • Reactome Reaction: BTK → NCK1 (indirect_complex)
  • Reactome Reaction: NCK1 → PLCG1 (indirect_complex)
  • Reactome Reaction: BTK → IGLC7 (indirect_complex)
  • Reactome Reaction: VAV1 → IGLC6 (indirect_complex)
  • Reactome Reaction: PLCG1 → VAV1 (indirect_complex)
  • Reactome Reaction: SHC1 → CBLB (indirect_complex)
  • Reactome Reaction: VAV1 → BLNK (indirect_complex)
  • Reactome Reaction: GRB2 → VAV1 (indirect_complex)
  • Reactome Reaction: CBL → PLCG2 (indirect_complex)
  • Reactome Reaction: PLCG1 → DAPP1 (indirect_complex)
  • Reactome Reaction: BTK → SHC1 (indirect_complex)
  • Reactome Reaction: GRB2 → PIK3R1 (indirect_complex)
  • Reactome Reaction: GRB2 → SHC1 (indirect_complex)
  • Reactome Reaction: IGKC → DAPP1 (indirect_complex)
  • Reactome Reaction: NCK1 → SOS1 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC2 (indirect_complex)
  • Reactome Reaction: BTK → CBL (indirect_complex)
  • Reactome Reaction: GRB2 → NCK1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → NCK1 (indirect_complex)
  • Reactome Reaction: PLCG1 → SOS1 (indirect_complex)
  • Reactome Reaction: BTK → IGLC2 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC2 (indirect_complex)
  • Reactome Reaction: NCK1 → VAV1 (direct_complex)
  • Reactome Reaction: PLCG2 → DAPP1 (indirect_complex)
  • Reactome Reaction: IGHD → DAPP1 (indirect_complex)
  • Reactome Reaction: NCK1 → IGLC7 (indirect_complex)
  • Reactome Reaction: BTK → CD79B (indirect_complex)
  • Reactome Reaction: DAPP1 → IGLC1 (indirect_complex)
  • Reactome Reaction: PLCG1 → CBLB (indirect_complex)
  • Reactome Reaction: BTK → PLCG1 (indirect_complex)
  • Reactome Reaction: BTK → BLNK (indirect_complex)
  • Reactome Reaction: PLCG2 → VAV1 (indirect_complex)
  • Reactome Reaction: PLCG2 → SOS1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PLCG1 (indirect_complex)
  • Reactome Reaction: IGHM → VAV1 (indirect_complex)
  • Reactome Reaction: PLCG2 → IGLC6 (indirect_complex)
  • Reactome Reaction: DAPP1 → IGLC7 (indirect_complex)
  • Reactome Reaction: IGHM → NCK1 (indirect_complex)
  • Reactome Reaction: CD79A → DAPP1 (indirect_complex)
  • Reactome Reaction: GRB2 → PIK3CD (indirect_complex)
  • Reactome Reaction: IGHD → NCK1 (indirect_complex)
  • Reactome Reaction: DAPP1 → BLNK (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC7 (indirect_complex)
  • Reactome Reaction: BTK → PLCG2 (indirect_complex)
  • Reactome Reaction: DAPP1 → CBLB (indirect_complex)
  • Reactome Reaction: NCK1 → IGLC2 (indirect_complex)
  • Reactome Reaction: BTK → CD79A (indirect_complex)
  • Reactome Reaction: PLCG2 → IGLC2 (indirect_complex)
  • Reactome Reaction: IGHD → SHC1 (indirect_complex)
  • Reactome Reaction: IGKC → SHC1 (indirect_complex)
  • Reactome Reaction: SOS1 → DAPP1 (indirect_complex)
  • Reactome Reaction: VAV1 → CBLB (indirect_complex)
  • Reactome Reaction: CD19 → PIK3R1 (indirect_complex)
  • Reactome Reaction: CD19 → PIK3CD (indirect_complex)
  • Reactome Reaction: GRB2 → VAV1 (direct_complex)
  • Reactome Reaction: PLCG2 → IGLC7 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGHD → PLCG1 (indirect_complex)
  • Reactome Reaction: PLCG2 → CBLB (indirect_complex)
  • Reactome Reaction: IGKC → PLCG2 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → NCK1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PLCG1 (indirect_complex)
  • Reactome Reaction: CD19 → GRB2 (direct_complex)
  • Reactome Reaction: CBL → DAPP1 (indirect_complex)
  • Reactome Reaction: SYK → PLCG1 (indirect_complex)
  • Reactome Reaction: CD79A → PLCG1 (indirect_complex)
  • Reactome Reaction: CD79A → VAV1 (indirect_complex)
  • Reactome Reaction: NCK1 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: PLCG1 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC7 (indirect_complex)
  • Reactome Reaction: SYK → PLCG2 (indirect_complex)
  • Reactome Reaction: BTK → VAV1 (indirect_complex)
  • Reactome Reaction: SOS1 → SHC1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → VAV1 (indirect_complex)
  • Reactome Reaction: BTK → CBLB (indirect_complex)
  • Reactome Reaction: BTK → GRB2 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC6 (indirect_complex)
  • Reactome Reaction: CBL → VAV1 (indirect_complex)
  • Reactome Reaction: IGHD → PLCG2 (indirect_complex)
  • Reactome Reaction: NCK1 → BLNK (indirect_complex)
  • Reactome Reaction: VAV1 → IGLC1 (indirect_complex)
  • Reactome Reaction: CBL → NCK1 (indirect_complex)
  • Reactome Reaction: BTK → IGLC3 (indirect_complex)
  • Reactome Reaction: VAV1 → SHC1 (direct_complex)
  • Reactome Reaction: IGHM → PLCG2 (indirect_complex)
  • Reactome Reaction: CBL → SHC1 (indirect_complex)
  • Reactome Reaction: SH3KBP1 → DAPP1 (indirect_complex)
  • Reactome Reaction: IGKC → VAV1 (indirect_complex)
  • Reactome Reaction: CD79A → NCK1 (indirect_complex)
  • Reactome Reaction: VAV1 → IGLC2 (indirect_complex)
  • Reactome Reaction: NCK1 → DAPP1 (indirect_complex)
  • Reactome Reaction: PLCG2 → IGLC3 (indirect_complex)
  • Reactome Reaction: NCK1 → IGLC6 (indirect_complex)
  • Reactome Reaction: BTK → SH3KBP1 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC1 (indirect_complex)
  • Reactome Reaction: BTK → IGLC6 (indirect_complex)
  • Reactome Reaction: IGKC → NCK1 (indirect_complex)
  • Reactome Reaction: CD79B → PLCG1 (indirect_complex)
  • Reactome Reaction: VAV1 → DAPP1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → SHC1 (indirect_complex)
  • Reactome Reaction: BTK → SOS1 (indirect_complex)
  • Reactome Reaction: CBL → PLCG1 (indirect_complex)
  • Reactome Reaction: CD19 → VAV1 (direct_complex)
  • Reactome Reaction: NCK1 → IGLC3 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC3 (indirect_complex)
  • Reactome Reaction: DAPP1 → IGLC2 (indirect_complex)
  • Reactome Reaction: BTK → DAPP1 (indirect_complex)
  • Reactome Reaction: CD79B → PLCG2 (indirect_complex)
  • Reactome Reaction: PLCG1 → SHC1 (indirect_complex)
  • Reactome Reaction: IGHM → SHC1 (indirect_complex)
  • Reactome Reaction: VAV1 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → SHC1 (indirect_complex)
  • Reactome Reaction: BTK → IGHD (indirect_complex)
  • Reactome Reaction: CD79B → SHC1 (indirect_complex)
  • Reactome Reaction: GRB2 → PLCG1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PLCG2 (indirect_complex)
  • Reactome Reaction: GRB2 → PLCG2 (indirect_complex)
  • Reactome Reaction: SH3KBP1 → SHC1 (indirect_complex)
In total, 193 gene pairs are associated to this article in curated databases