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UV-Induced Tyrosine Phosphorylation of PKCδ and Promotion of Apoptosis in the HaCaT Cell Line

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Abstract

Protein kinase C δ (PKCδ) is activated through tyrosine phosphorylation and is involved in apoptosis induction in the H2O2-treated fibroblasts. In the human keratinocyte HaCaT cell line, ultraviolet radiation, which induces apoptosis, promoted tyrosine phosphorylation and activation of PKCδ, but neither enhanced threonine phosphorylation in the activation loop nor generated the catalytic fragment of the PKC isoform. Tyrosine phosphorylation of PKCδ was prevented by a radical scavenger, N-acetyl-l-cysteine, and by a tyrosine kinase inhibitor, genistein, in the ultraviolet-irradiated keratinocyte cell line. Ultraviolet radiation-induced apoptosis was attenuated by N-acetyl-l-cysteine and genistein as well as by a PKC inhibitor, bisindolylmaleimide I. These results indicate that reactive oxygen species generated by ultraviolet radiation enhance tyrosine phosphorylation of PKCδ, and the PKC isoform thus activated by the modification reaction contributes to induction of apoptotic cell death in keratinocytes.

References (37)

  • C. Sachsenmaier et al.

    Involvement of growth factor receptors in the mammalian UVC response

    Cell

    (1994)
  • M. Kato et al.

    Ultraviolet light induces redox reaction-mediated dimerization and superactivation of oncogenic Ret tyrosine kinases

    Mol. Biol. Cell

    (2000)
  • D.R. Alessi et al.

    Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα

    Curr. Biol.

    (1997)
  • L. Stempka et al.

    Phosphorylation of protein kinase Cδ (PKCδ) at threonine 505 is not a prerequisite for enzymatic activity. Expression of rat PKCδ and an alanine 505 mutant in bacteria in a functional form

    J. Biol. Chem.

    (1997)
  • H.R. Griffiths et al.

    Molecular and cellular effects of ultraviolet light-induced genotoxicity

    Crit. Rev. Clin. Lab. Sci.

    (1998)
  • Y. Nishizuka

    Protein kinase C and lipid signaling for sustained cellular responses

    FASEB J.

    (1995)
  • M. Gschwendt

    Protein kinase C δ

    Eur. J. Biochem.

    (1999)
  • S.H. Yuspa et al.

    Role of oncogenes and tumor suppressor genes in multistage carcinogenesis

    J. Invest. Dermatol.

    (1994)
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    Abbreviations used: BIM, bisindolylmaleimide I; CHO, Chinese hamster ovary; NAC, N-acetyl-l-cysteine; PBS, phosphate-buffered saline; PI, phosphatidylinositol; PKC, protein kinase C; ROS, reactive oxygen species.

    1

    To whom correspondence and reprint requests should be addressed at Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan. Fax: 81-78-803-5972. E-mail: [email protected].

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