Gene interactions and pathways from curated databases and text-mining
Cell Signal 2000, PMID: 10704825

Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains.

Bone, H; Welham, M J

p46(Shc) and p52(Shc) become heavily tyrosine phosphorylated in response to interleukin 3 (IL-3) treatment. We have investigated the potential of Shc to integrate IL-3 signalling pathways and demonstrate that Shc associates with the beta subunits of the human (betac) and murine (Aic2A) IL-3 receptors, SHIP and Gab2 following IL-3 stimulation. The interaction between Shc and the IL-3 receptor beta chains was direct, mediated by both the SH2 and PTB domains. Interaction with SHIP was via the Shc PTB domain and the Shc SH2 domain mediated the interaction with Gab2. Phosphopeptide competition studies suggest that the SH2 domain interacts primarily with tyrosine 612 of betac (610 of Aic2A), and the PTB domain with tyrosine 577 of betac (575 of Aic2A). PTB binding to IL-3R beta chains was of highest affinity, and appeared to play the primary role in binding. These findings suggest that Shc may play an important role in coordinately integrating IL-3 signalling pathways.

Diseases/Pathways annotated by Medline MESH: Leukemia, Erythroblastic, Acute
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Text Mining Data

Shc → IL-3: " Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation "

Manually curated Databases

  • IRef Biogrid Interaction: CSF2RB — SHC1 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: SHC1 — INPP5D (in vivo)
  • IRef Hprd Interaction: SHC1 — INPP5D (in vitro)
  • IRef Hprd Interaction: SHC1 — CSF2RB (in vitro)
  • IRef Hprd Interaction: SHC1 — GAB2 (in vitro)
  • IRef Hprd Interaction: SHC1 — GAB2 (in vivo)
  • IRef Intact Interaction: SHC1 — INPP5D (direct interaction, pull down)
  • IRef Intact Interaction: CSF2RB — SHC1 (association, coimmunoprecipitation)
  • IRef Intact Interaction: SHC1 — GAB2 (direct interaction, pull down)
  • IRef Intact Interaction: SHC1 — GAB2 (physical association, coimmunoprecipitation)
  • IRef Ophid Interaction: SHC1 — GAB2 (aggregation, confirmational text mining)
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → SHIP (INPP5D) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/SHIP complex (CSF2RB-JAK2-SHC1-INPP5D-IL3-IL3RA) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: SHIP (INPP5D) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/SHIP complex (CSF2RB-JAK2-SHC1-INPP5D-IL3-IL3RA) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → GRB2/GAB2 complex (GRB2-GAB2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC/GRB2/GAB2 complex (CSF2RB-JAK2-SHC1-GRB2-GAB2-IL3-IL3RA) → GRB2/GAB2 complex (GRB2-GAB2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2 complex (CSF2RB-JAK2-IL3-IL3RA) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2/SHC complex (CSF2RB-JAK2-SHC1-IL3-IL3RA) → SHC (SHC1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL3-mediated signaling events: IL3/IL3RA/CSF2RB (dodecamer)/JAK2/JAK2 complex (CSF2RB-JAK2-IL3-IL3RA) → SHC (SHC1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
In total, 34 gene pairs are associated to this article in curated databases