Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes.
Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes.
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DOI：
10.1038/onc.2010.540
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发表时间：
2011-03-31
期刊：
影响因子：
8
通讯作者：
Bollag, W. B.
中科院分区：
文献类型：
--
作者：
Arun, S. N.;Kaddour-Djebbar, I.;Shapiro, B. A.;Bollag, W. B.
我们以前的研究表明，蛋白激酶D（PKD），一种参与各种细胞过程的丝氨酸/苏氨酸激酶，在基底细胞癌（BCC）中上调，支持PKD在皮肤中可能的致瘤作用。由于BCC的最大危险因素是阳光照射，因此研究了紫外线B（UVB）照射激活原代小鼠角质形成细胞中PKD的能力。使用两个自磷酸化特异性抗体的Western分析，我们首次表明UVB以时间和剂量依赖性方式激活PKD。UVB诱导的PKD活化使用体外激酶测定进行验证。此外，抗氧化剂预处理减少了激活，这表明与氧化应激有关。UVB诱导的PKD活化主要由Src家族酪氨酸激酶介导，而不是蛋白激酶C（PKC），事实上，UVB并不改变PKC介导的转磷酸化。UVB剂量依赖性地诱导细胞凋亡，这种死亡可以通过过度表达野生型PKD来阻止，但不能通过突变型PKD或空腺病毒来阻止。事实上，突变体，不能被Src激酶磷酸化加剧UVB引起的细胞凋亡。因此，我们的数据表明，UVB照射角质形成细胞诱导Src介导的PKD活化，从而保护细胞免受UVB刺激的凋亡，为观察到的BCC中PKD上调提供了一个可能的解释。
Our previous studies demonstrated that protein kinase D (PKD), a serine/threonine kinase implicated in various cell processes, is up-regulated in basal cell carcinoma (BCC), supporting a possible tumorigenic role for PKD in skin. Since 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 up-regulation of PKD in BCC.
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DOI：
10.1016/s0006-291x(03)00345-0
发表时间：
2003-03-28
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
10.3
作者：
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通讯作者：
Bollag, WB
影响因子：
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作者：
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