UVB-induced activation and internalization of keratinocyte growth factor receptor

Cinzia Marchese, Vittoria Maresca, Giorgia Cardinali, Francesca Belleudi, Simona Ceccarelli, Marinella Bellocci, Luigi Frati, Maria Rosaria Torrisi, Mauro Picardo

Research output: Contribution to journalArticle

Abstract

Ultraviolet irradiation of mammalian cells induces several events that include activation of growth factor receptors and triggering of signal transduction pathway. Most of the UV responses are mediated by the production of reactive oxygen species (ROS) and can be blocked by antioxidants. In this study, we analysed the effect of UVB irradiation at physiologic doses and that of the prooxidant agent cumene hydroperoxide (CUH) on the activation of the receptor for keratinocyte growth factor (KGF), a key mediator of epithelial growth and differentiation. Exposure to both UVB (30-150 mJ/cm2) and CUH (200 μM of NIH3T3 KGFR (KGF receptors) transfectants caused a rapid tyrosine phosphorylation and activation of KGFR similar to that induced by KGF, and internalization of the activated receptor. The KGFR expression appeared unmodified by the treatments. Ultrastructural observations of both UVB- and CUH-treated cells showed a normal morphology of the plasma membranes and intracellular organelles. The antioxidant N-acetylcysteine inhibited UVB-induced receptor phosphorylation. The generation of an intracellular oxidative stress was detected as a decrease of catalase activity and of vitamin E, and reduced glutathione levels, whereas superoxide dismutase activity was not significantly modified. A peroxidation of polyunsaturated fatty acids of cell membranes was observed after both treatments, associated with the intracellular oxidative stress. Similar biochemical events were observed on NIH3T3 untransfected control cells, suggesting that KGFR activation follows intracellular generation of ROS and is not associated with a scavenging effect. Taken together our results demonstrate that exposure to UVB and to oxidant stimuli induces a rapid intracellular production of ROS, which in turn are capable of triggering KGFR activation and internalization, similar to those induced by KGF.

Original languageEnglish
Pages (from-to)2422-2431
Number of pages10
JournalOncogene
Volume22
Issue number16
DOIs
Publication statusPublished - Apr 24 2003

Keywords

  • Keratinocyte growth factor receptor
  • Oxidative stress
  • Tyrosine phosphorylation
  • UVB

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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  • Cite this

    Marchese, C., Maresca, V., Cardinali, G., Belleudi, F., Ceccarelli, S., Bellocci, M., Frati, L., Torrisi, M. R., & Picardo, M. (2003). UVB-induced activation and internalization of keratinocyte growth factor receptor. Oncogene, 22(16), 2422-2431. https://doi.org/10.1038/sj.onc.1206301