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

被引：22
作者：
Arun, S. N. [2 ]
Kaddour-Djebbar, I. [3 ]
Shapiro, B. A. [2 ]
Bollag, W. B. [1 ,2 ,3 ,4 ,5 ]
机构：
[1] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA
[2] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA
[3] Charlie Norwood VA Med Ctr, Augusta, GA USA
[4] Med Coll Georgia, Dept Med, Augusta, GA 30912 USA
[5] Med Coll Georgia, Dept Dermatol, Augusta, GA 30912 USA
来源：
ONCOGENE | 2011年 / 30卷 / 13期
基金：
美国国家卫生研究院;
关键词：
apoptosis; epidermis; protein kinase C; protein kinase D; skin; Src; NF-KAPPA-B; RADIATION-INDUCED APOPTOSIS; POTENTIATES DNA-SYNTHESIS; D-DEPENDENT ACTIVATION; G(Q)-COUPLED RECEPTORS; LOOP PHOSPHORYLATION; SKIN-CANCER; C-MU; PROLIFERATION; EXPRESSION;
D O I：
10.1038/onc.2010.540
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. Oncogene (2011) 30, 1586-1596; doi: 10.1038/onc.2010.540; published online 6 December 2010
引用
收藏
页码：1586 / 1596
页数：11
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