Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1991, PMID: 2022652

Internalization and down-regulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminal tyrosines.

Helin, K; Beguinot, L

The C terminus of the epidermal growth factor receptor (EGF-R) contains three tyrosines (Y1068, Y1148, and Y1173) which correspond to the major autophosphorylation sites. To investigate the role of the tyrosines in internalization and down-regulation of the EGF-R, mutational analysis was performed with receptors in which 1, 2, or all 3 tyrosines were changed to phenylalanines. The triple point mutant EGF-R, expressed in NIH-3T3, exhibited low autophosphorylation in vivo, low biological and reduced kinase activities. Single and double point mutants were down-regulated, as well as wild type EGF-R in response to EGF showing a half-life of about 1 h. Degradation of the triple point mutant, however, was impaired and resulted in a half-life of 4 h in the presence of EGF. EGF-dependent down-regulation of surface receptors was decreased in the triple point mutant EGF-R as was internalization and degradation of EGF. The specific rate of internalization of the triple point mutant was reduced. By contrast, intracellular processing of ligand previously internalized at 20 degrees C was similar between wild type and mutant receptors. Taken together the data indicate that the delay in degradation observed in cells expressing the triple point mutant EGF-R can be attributed mainly to a slower removal from the cell surface. Our results show that in the full-length EGF-R all three C-terminal tyrosines are necessary for rapid internalization, suggesting that autophosphorylation is required for efficient EGF-dependent receptor endocytosis.

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Manually curated Databases

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