Extracellular generation of hydrogen peroxide is responsible for activation of EGF receptor by ultraviolet A radiation.
Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) have been proposed to be activated in cells exposed to ultraviolet A (UVA) radiation (320-400 nm) and to be involved in photocarcinogenesis. Singlet oxygen and hydrogen peroxide are being discussed as mediators of the activation of signal transduction pathways by UVA. It is demonstrated here that EGFR is not activated in cells exposed to UVA in the absence of extracellular photosensitizers. Rather, UVA was capable of activating the EGFR and the related ErbB2 receptor tyrosine kinase in HeLa cells and human keratinocytes only under conditions that allowed for the extracellular photochemical generation of H(2)O(2), such as when cells were covered with cell culture medium during exposure to UVA. Pretreatment of cells with vanadate was required for UVA-induced EGFR activation, pointing to the involvement of protein tyrosine phosphatases. Unlike H(2)O(2), photochemically generated singlet oxygen did not activate EGFR but instead impaired the activation of EGFR by its ligand, EGF. In summary, extracellularly generated H(2)O(2) mediates UVA-induced activation of the EGFR and of ErbB2, whereas intracellular generation of reactive oxygen species upon exposure of cells to UVA is not sufficient for activation of the receptor.
von Montfort
Claudia
C
Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Germany.
Fernau
Niklas S
NS
Beier
Juliane I
JI
Sies
Helmut
H
Klotz
Lars-Oliver
LO
D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016877:Oxidants / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D010787:Photosensitivity Disorders; D017382:Reactive Oxygen Species / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction; D026082:Singlet Oxygen / Q000378:metabolism; D014466:Ultraviolet Rays
D066246:ErbB Receptors; D006861:Hydrogen Peroxide; D016877:Oxidants; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; D026082:Singlet Oxygen