H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation

Dominik Peus, Alexander Meves, Remus A. Vasa, Astrid Beyerle, Timothy O'Brien, Mark R. Pittelkow

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Ultraviolet radiation (UVR)-induced receptor phosphorylation is increasingly recognized as a widely occurring phenomenon. However, the mechanisms, mediators, and sequence of events involved in this process remain ill-defined. We have recently shown that exposure of human keratinocytes to physiologic doses of ultraviolet B radiation (UVB) activates epidermal growth factor receptor (EGFR)/extracellular-regulated kinase 1 and 2 (ERK1/2), and p38 signaling pathways via reactive oxygen species. Here we demonstrate that UVB exposure increased intra- and extracellular H2O2 production rapidly in a time-dependent manner. An EGFR-specific monoclonal antibody abrogated EGFR autophosphorylation and markedly decreased the phosphorylation of ERK1/2 whereas p38 activation was unaffected. Overexpression of catalase strongly inhibited UVB-induced EGFR/ERK1/2 pathway activation. These findings establish the sequence of events after UVB irradiation: (i) H2O2 generation, (ii) EGFR phosphorylation, and (iii) ERK activation. Our results identify UVB-induced H2O2 as a second messenger that is required for EGFR and dependent downstream signaling pathways activation. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)1197-1202
Number of pages6
JournalFree Radical Biology and Medicine
Volume27
Issue number11-12
DOIs
StatePublished - Dec 1 1999

Keywords

  • EGF receptor
  • Extracellular-regulated signaling kinase
  • Free radicals
  • Hydrogen peroxide
  • Mitogen-activated protein kinase
  • Ultraviolet radiation
  • p38

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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