Epidermal growth factor receptor is modulated by redox through multiple mechanisms. Effects of reductants and H2O2

Hideaki Kamata, Yukinao Shibukawa, Shin Ichi Oka, Hajime Hirata

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


The cellular redox state has been shown to play an essential role in cellular signaling systems. Here we investigate the effects of reductants and H2O2 on the signaling of epidermal growth factor (EGF) in cells, H2O2 induced the phosphorylation of the EGF receptor and the formation of a receptor complex comprising Shc, Grb2, Sos, and the EGF receptor. Dimerization or oligomerization of the EGF receptor was not induced by H2O2. Protein tyrosine phosphatase (PTP) assay showed that H2O2 suppressed dephosphorylation of the EGF receptor in cell lysates, suggesting that inactivation of PTP was involved in H2O2-induced activation of the EGF receptor. In contrast, the reductants N-acetyl-L-cysteine [Cys(Ac)] and dithiothreitol markedly suppressed EGF-induced dimerization and activation of the EGF receptor in cells. In accordance with suppression of the EGF receptor. Cys(Ac) suppressed EGF-induced activation of Ras, phosphatidylinositol 3-kinase and mitogen-activated protein kinase. Dithiothreitol completely inhibited EGF binding and kinase activation of the EGF receptor both in vitro and in vivo. In contrast, Cys(Ac) suppressed high- affinity EGF-binding sites on the cells, but had no effect on low-affinity binding sites. Furthermore. Cys (Ac) did not suppress EGF-induced kinase activation or dimerization of the EGF receptor in vitro, indicating that it suppressed the EGF receptor through a redox-sensitive cellular process or processes. Thus, the EGF receptor is regulated by redox through multiple steps including dephosphorylation by PTP, ligand binding, and a Cys(Ac)- sensitive cellular process or processes.

Original languageEnglish (US)
Pages (from-to)1933-1944
Number of pages12
JournalEuropean Journal of Biochemistry
Issue number7
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry


  • Epidermal growth factor receptor
  • HO
  • N-acetyl-L-cysteine
  • Redox


Dive into the research topics of 'Epidermal growth factor receptor is modulated by redox through multiple mechanisms. Effects of reductants and H2O2'. Together they form a unique fingerprint.

Cite this