UV activates growth factor receptors via reactive oxygen intermediates.
Exposure of mammalian cells to UV irradiation induces rapid and transient expression of early growth response-1 gene (Egr-1) encoding a transcription factor that plays a role in cell survival. These signals from the irradiated cell surface are likely to involve more than one pathway, 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. EGFR activation by irradiation of cells is abrogated by suramin, by antioxidants, and by the presence of a dominant negative EGFR. UV induces the formation of complexes between activated EGFR and SOS, Grb2, PLC gamma, and SHC that can be precipitated with antibodies to EGFR. The activation of EGFR by UV is mimicked by H2O2, suggesting that ROI may function upstream of EGFR activation. Our observations support the hypothesis that ROI and growth factor receptors operate in the early steps of the UV signal that lead to the enhanced expression and activity of Egr-1.
Huang
R P
RP
La Jolla Cancer Research Foundation, California 92037, USA.
Wu
J X
JX
Fan
Y
Y
Adamson
E D
ED
D016475:3T3 Cells; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D051766:Early Growth Response Protein 1; D004848:Epithelium; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006133:Growth Substances / Q000494:pharmacology; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D017382:Reactive Oxygen Species; D017978:Receptors, Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000528:radiation effects*; D013498:Suramin / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D014466:Ultraviolet Rays
D000975:Antioxidants; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D006133:Growth Substances; D017874:Immediate-Early Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; D017978:Receptors, Growth Factor; D013859:Thiocarbamates; D014157:Transcription Factors; C066229:prolinedithiocarbamate; D014443:Tyrosine; D013498:Suramin; D011392:Proline; D066246:ErbB Receptors