Gene interactions and pathways from curated databases and text-mining
J Cell Sci 2004, PMID: 15564375

FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity.

Li, Xuan; Brunton, Valerie G; Burgar, Helen R; Wheldon, Lee M; Heath, John K

Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human Sprouty 2 (hSpry2) on residue Y55. This event requires the presence of the signalling adaptor fibroblast growth factor receptor substrate 2 (FRS2). The phosphorylation of hSpry2 is therefore mediated by an intermediate kinase. Using a SRC family kinase-specific inhibitor and mutant cells, we show that hSpry2 is a direct substrate for SRC family kinases, including SRC itself. Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity. SRC forms a complex with hSpry2 and this interaction is enhanced by hSpry2 phosphorylation. Phosphorylation of hSpry2 is required for hSpry2 to inhibit activation of the extracellular signal-regulated kinase pathway. These results show that recruitment of SRC to FRS2 leads to activation of signal attenuation pathways.

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Text Mining Data

ERK ⊣ fibroblast growth factor receptor: " FRS2 dependent SRC activation is required for fibroblast growth factor receptor induced phosphorylation of Sprouty and suppression of ERK activity "

SRC → FRS2: " FRS2 dependent SRC activation is required for fibroblast growth factor receptor induced phosphorylation of Sprouty and suppression of ERK activity "

fibroblast growth factor receptor → SRC: " FRS2 dependent SRC activation is required for fibroblast growth factor receptor induced phosphorylation of Sprouty and suppression of ERK activity "

fibroblast growth factor receptor → FRS2: " FRS2 dependent SRC activation is required for fibroblast growth factor receptor induced phosphorylation of Sprouty and suppression of ERK activity "

SRC → FRS2: " Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity "

SRC → fibroblast growth factor: " Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity "

SRC → fibroblast growth factor receptor: " Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity "

Manually curated Databases

  • NCI Pathway Database FGF signaling pathway: Src (SRC) → Sprouty2 (SPRY2) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FGF signaling pathway: Src (SRC) → FGFR/FGF/Syndecan-2/FRS2 complex (SDC2-FRS2) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FGF signaling pathway: Src (SRC) → FGFR/FGF/Syndecan-2/FRS2/Sprouty2 complex (SDC2-FRS2-SPRY2) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FGF signaling pathway: Sprouty2 (SPRY2) → FGFR/FGF/Syndecan-2/FRS2 complex (SDC2-FRS2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FGF signaling pathway: Sprouty2 (SPRY2) → FGFR/FGF/Syndecan-2/FRS2/Sprouty2 complex (SDC2-FRS2-SPRY2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FGF signaling pathway: FGFR/FGF/Syndecan-2/FRS2 complex (SDC2-FRS2) → FGFR/FGF/Syndecan-2/FRS2/Sprouty2 complex (SDC2-FRS2-SPRY2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • Reactome Reaction: PPP2CB → SRC (reaction)
  • Reactome Reaction: PPP2CA → SPRY2 (indirect_complex)
  • Reactome Reaction: SPRY2 → SRC (reaction)
  • Reactome Reaction: PPP2CA → SRC (reaction)
  • Reactome Reaction: PPP2R1A → SPRY2 (indirect_complex)
  • Reactome Reaction: PPP2R1A → SRC (reaction)
  • Reactome Reaction: PPP2CB → SPRY2 (indirect_complex)
In total, 15 gene pairs are associated to this article in curated databases