Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1995, PMID: 8530511

Dominant-negative mutants of Grb2 induced reversal of the transformed phenotypes caused by the point mutation-activated rat HER-2/Neu.

Xie, Y; Pendergast, A M; Hung, M C

To clarify the role of the Shc-Grb2-Sos trimer in the oncogenic signaling of the point mutation-activated HER-2/neu receptor tyrosine kinase (named p185), we interfered with the protein-protein interactions in the Shc.Grb2.Sos complex by introducing Grb2 mutants with deletions in either amino- (delta N-Grb2) or carboxyl-(delta C-Grb2) terminal SH3 domains into B104-1-1 cells derived from NIH3T3 cells expressing the point mutation-activated HER-2/neu. We found that the transformed phenotypes of the B104-1-1 cells were largely reversed by the delta N-Grb2. The effect of the delta C-Grb2 was much weaker. Biochemical analysis showed that the delta N-Grb2 was able to associate Shc but not p185 or Sos, while the delta C-Grb2 bound to Shc, p185, and Sos. The p185-mediated Ras activation was severely inhibited by the delta N-Grb2 but not the delta C-Grb2. Taken together, these data demonstrate that interruption of the interaction between Shc and the endogenous Grb2 by the delta N-Grb2 impairs the oncogenic signaling of the activated p185, indicating that (i) the delta N-Grb2 functions as a strong dominant-negative mutant, and (ii) Shc/Grb2/Sos pathway plays a major role in mediating the oncogenic signal of the activated p185. Unlike the delta N-Grb2, delta C-Grb2 appears to be a relatively weak dominant-negative mutant, probably due to its ability to largely fulfill the biological functions of the wild-type Grb2.

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Text Mining Data

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Manually curated Databases

  • Reactome Reaction: ERBB3 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → ERBB4 (reaction)
  • Reactome Reaction: BTC → GRB2 (reaction)
  • Reactome Reaction: NRAS → ERBB4 (reaction)
  • Reactome Reaction: GRB2 → KRAS (reaction)
  • Reactome Reaction: BTC → HRAS (reaction)
  • Reactome Reaction: EREG → GRB2 (indirect_complex)
  • Reactome Reaction: KRAS → ERBB4 (reaction)
  • Reactome Reaction: NRG2 → KRAS (reaction)
  • Reactome Reaction: SHC1 → SOS1 (indirect_complex)
  • Reactome Reaction: BTC → GRB2 (indirect_complex)
  • Reactome Reaction: GRB2 → NRG1 (indirect_complex)
  • Reactome Reaction: BTC → NRAS (reaction)
  • Reactome Reaction: SOS1 → ERBB4 (reaction)
  • Reactome Reaction: EGF → SOS1 (reaction)
  • Reactome Reaction: EGFR → NRAS (reaction)
  • Reactome Reaction: EGF → HRAS (reaction)
  • Reactome Reaction: EGF → KRAS (reaction)
  • Reactome Reaction: BTC → SOS1 (indirect_complex)
  • Reactome Reaction: EGFR → GRB2 (indirect_complex)
  • Reactome Reaction: ERBB3 → GRB2 (reaction)
  • Reactome Reaction: KRAS → SHC1 (reaction)
  • Reactome Reaction: HBEGF → HRAS (reaction)
  • Reactome Reaction: GRB2 → NRG4 (reaction)
  • Reactome Reaction: NRG4 → KRAS (reaction)
  • Reactome Reaction: NRG2 → SOS1 (reaction)
  • Reactome Reaction: ERBB3 → SOS1 (indirect_complex)
  • Reactome Reaction: ERBB3 → GRB2 (indirect_complex)
  • Reactome Reaction: ERBB3 → KRAS (reaction)
  • Reactome Reaction: EGFR → GRB2 (reaction)
  • Reactome Reaction: HRAS → ERBB4 (reaction)
  • Reactome Reaction: NRAS → NRG1 (reaction)
  • Reactome Reaction: KRAS → SOS1 (reaction)
  • Reactome Reaction: GRB2 → SHC1 (indirect_complex)
  • Reactome Reaction: HBEGF → SOS1 (reaction)
  • Reactome Reaction: NRAS → SHC1 (reaction)
  • Reactome Reaction: NRG2 → NRAS (reaction)
  • Reactome Reaction: EREG → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → NRG2 (indirect_complex)
  • Reactome Reaction: EGF → GRB2 (reaction)
  • Reactome Reaction: SOS1 → ERBB4 (indirect_complex)
  • Reactome Reaction: EGF → NRAS (reaction)
  • Reactome Reaction: EGFR → HRAS (reaction)
  • Reactome Reaction: GRB2 → HBEGF (indirect_complex)
  • Reactome Reaction: ERBB2 → NRAS (reaction)
  • Reactome Reaction: ERBB2 → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → NRAS (reaction)
  • Reactome Reaction: HRAS → SOS1 (reaction)
  • Reactome Reaction: EREG → KRAS (reaction)
  • Reactome Reaction: NRAS → SOS1 (reaction)
  • Reactome Reaction: SOS1 → NRG1 (indirect_complex)
  • Reactome Reaction: EREG → HRAS (reaction)
  • Reactome Reaction: HBEGF → NRAS (reaction)
  • Reactome Reaction: ERBB2 → KRAS (reaction)
  • Reactome Reaction: BTC → KRAS (reaction)
  • Reactome Reaction: SHC1 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → NRG1 (reaction)
  • Reactome Reaction: GRB2 → NRG4 (indirect_complex)
  • Reactome Reaction: GRB2 → HBEGF (reaction)
  • Reactome Reaction: GRB2 → ERBB4 (indirect_complex)
  • Reactome Reaction: NRG2 → HRAS (reaction)
  • Reactome Reaction: ERBB3 → NRAS (reaction)
  • Reactome Reaction: EGFR → KRAS (reaction)
  • Reactome Reaction: ERBB2 → GRB2 (indirect_complex)
  • Reactome Reaction: HRAS → SHC1 (reaction)
  • Reactome Reaction: GRB2 → HRAS (reaction)
  • Reactome Reaction: HRAS → NRG1 (reaction)
  • Reactome Reaction: EGFR → SOS1 (reaction)
  • Reactome Reaction: ERBB2 → HRAS (reaction)
  • Reactome Reaction: EREG → SOS1 (reaction)
  • Reactome Reaction: ERBB2 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → NRG2 (reaction)
  • Reactome Reaction: GRB2 → SHC1 (reaction)
  • Reactome Reaction: NRG4 → NRAS (reaction)
  • Reactome Reaction: NRG4 → HRAS (reaction)
  • Reactome Reaction: NRG2 → SOS1 (indirect_complex)
  • Reactome Reaction: BTC → SOS1 (reaction)
  • Reactome Reaction: EGF → SOS1 (indirect_complex)
  • Reactome Reaction: HBEGF → SOS1 (indirect_complex)
  • Reactome Reaction: ERBB3 → HRAS (reaction)
  • Reactome Reaction: KRAS → NRG1 (reaction)
  • Reactome Reaction: NRG4 → SOS1 (indirect_complex)
  • Reactome Reaction: EGFR → SOS1 (indirect_complex)
  • Reactome Reaction: EGF → GRB2 (indirect_complex)
  • Reactome Reaction: SOS1 → NRG1 (reaction)
  • Reactome Reaction: EREG → NRAS (reaction)
  • Reactome Reaction: ERBB2 → GRB2 (reaction)
  • Reactome Reaction: HBEGF → KRAS (reaction)
  • Reactome Reaction: NRG4 → SOS1 (reaction)
  • Reactome Reaction: EREG → GRB2 (reaction)
In total, 66 gene pairs are associated to this article in curated databases