Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes

S. N. Arun, I. Kaddour-Djebbar, B. A. Shapiro, W. B. Bollag

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Our previous studies demonstrated that protein kinase D (PKD), a serine/threonine kinase implicated in various cell processes, is upregulated in basal cell carcinoma (BCC), supporting a possible tumorigenic role for PKD in skin. As the greatest risk factor for BCC is sun exposure, the ability of ultraviolet B (UVB) irradiation to activate PKD in primary mouse keratinocytes was investigated. Using western analysis with two autophosphorylation-specific antibodies, we show for the first time that UVB activated PKD in a time- and dose-dependent manner. UVB-induced PKD activation was verified using an in vitro kinase assay. Furthermore, activation was reduced by antioxidant pretreatment, suggesting a link with oxidative stress. UVB-induced PKD activation was mediated primarily by Src family tyrosine kinases rather than protein kinase C (PKC), and in fact, UVB did not alter PKC-mediated transphosphorylation. UVB induced apoptosis dose dependently, and this death could be prevented by overexpression of wild-type PKD, but not mutant PKD or the empty adenovirus. Indeed, a mutant that cannot be phosphorylated by Src kinases exacerbated UVB-elicited apoptosis. Thus, our data indicate that UVB irradiation of keratinocytes induces Src-mediated activation of PKD, which protects cells from UVB-stimulated apoptosis, providing a possible explanation for the observed upregulation of PKD in BCC.

Original languageEnglish (US)
Pages (from-to)1586-1596
Number of pages11
JournalOncogene
Volume30
Issue number13
DOIs
StatePublished - Mar 31 2011

Keywords

  • Src
  • apoptosis
  • epidermis
  • protein kinase C
  • protein kinase D
  • skin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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