H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation |
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Authors: | Dominik Peus Alexander Meves Remus A Vasa Astrid Beyerle Timothy OBrien Mark R Pittelkow |
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Institution: | Dominik Peus, Alexander Meves, Remus A. Vasa, Astrid Beyerle, Timothy O’Brien,Mark R. Pittelkow |
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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. |
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Keywords: | Ultraviolet radiation Hydrogen peroxide EGF receptor Mitogen-activated protein kinase Extracellular-regulated signaling kinase p38 Free radicals |
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