Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1999, PMID: 10092678

The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation.

Meakin, S O; MacDonald, J I; Gryz, E A; Kubu, C J; Verdi, J M

We have isolated a human cDNA for the signaling adapter molecule FRS-2/suc1-associated neurotrophic factor target and shown that it is tyrosine-phosphorylated in response to nerve growth factor (NGF) stimulation. Importantly, we demonstrate that the phosphotyrosine binding domain of FRS-2 directly binds the Trk receptors at the same phosphotyrosine residue that binds the signaling adapter Shc, suggesting a model in which competitive binding between FRS-2 and Shc regulates differentiation versus proliferation. Consistent with this model, FRS-2 binds Grb-2, Crk, the SH2 domain containing tyrosine phosphatase SH-PTP-2, the cyclin-dependent kinase substrate p13(suc1), and the Src homology 3 (SH3) domain of Src, providing a functional link between TrkA, cell cycle, and multiple NGF signaling effectors. Importantly, overexpression of FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal differentiation.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: FRS2 — NTRK3 (direct interaction, pull down)
  • IRef Biogrid Interaction: FRS2 — NTRK1 (direct interaction, pull down)
  • IRef Biogrid Interaction: FRS2 — NTRK1 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: PLCG1 — NTRK1 (direct interaction, pull down)
  • IRef Biogrid Interaction: FRS2 — NTRK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PLCG1 — NTRK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: SHC1 — NTRK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: SHC1 — NTRK3 (direct interaction, pull down)
  • IRef Biogrid Interaction: PLCG1 — NTRK3 (direct interaction, pull down)
  • IRef Biogrid Interaction: FRS2 — CRK (direct interaction, pull down)
  • IRef Biogrid Interaction: NTRK1 — SHC1 (direct interaction, pull down)
  • IRef Biogrid Interaction: FRS2 — GRB2 (direct interaction, pull down)
  • IRef Hprd Interaction: CRK — FRS2 (in vitro)
  • IRef Hprd Interaction: FRS2 — NTRK1 (in vitro)
  • IRef Hprd Interaction: SRC — FRS2 (in vitro)
  • IRef Ophid Interaction: NTRK1 — FRS2 (aggregation, confirmational text mining)
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: FRS2 family-active (FRS3/FRS2) → SHC (SHC1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: FRS2 family-active (FRS3/FRS2) → FRS2 family (FRS3/FRS2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: NGF/NGFR-active (NTRK1/NGF/NTF3/NTRK3/BDNF/NTRK2/NTF4/NTRK2) → SHC (SHC1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: NGF/NGFR-active (NTRK1/NGF/NTF3/NTRK3/BDNF/NTRK2/NTF4/NTRK2) → FRS2 family (FRS3/FRS2) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: SHC (SHC1) → FRS2 family (FRS3/FRS2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
In total, 32 gene pairs are associated to this article in curated databases