UV ACTIVATES GROWTH-FACTOR RECEPTORS VIA REACTIVE OXYGEN INTERMEDIATES

Exposure of mammalian cells to UV irradiation induces rapid and transi ent expression of early growth response-1 gene (Egr-1) encoding a tran scription factor that plays a role in cell survival. These signals fro m the irradiated cell surface are likely to involve more than one path way, and we show here that an essential pathway involves activation of several growth factor receptors by reactive oxygen intermediates (ROI ). UVC irradiation causes the tyrosine phosphorylation of EGF receptor (EGFR) in mouse NIH 3T3 fibroblasts and HC11 mouse mammary cells. EGF R activation by irradiation of cells is abrogated by suramin, by antio xidants, and by the presence of a dominant negative EGFR. UV induces t he formation of complexes between activated EGFR and SOS, Grb2, PLC ga mma, and SHC that can be precipitated with antibodies to EGFR. The act ivation of EGFR by UV is mimicked by H2O2, suggesting that ROI may fun ction upstream of EGFR activation. Our observations support the hypoth esis that ROI and growth factor receptors operate in the early steps o f the UV signal that lead to the enhanced expression and activity of E gr-1.