在不同亚细胞蛋白质激酶Cdelta站点的定位影响其proapoptotic和凋亡功能和独特的下游信号通路的激活。
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高美尔R,湘C,福克斯的年代,李港元,陆W, Okhrimenko H,布罗迪C
在不同亚细胞蛋白质激酶Cdelta站点的定位影响其proapoptotic和凋亡功能和独特的下游信号通路的激活。
摩尔癌症研究》2007年6月,5 (6):627 - 39。
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17579121 (在PubMed]
- 文摘
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蛋白激酶Cdelta (PKCdelta)调节细胞凋亡和生存在不同细胞系统。PKCdelta把不同亚细胞的网站针对凋亡刺激;然而,其亚细胞定位的作用在其proapoptotic和凋亡功能刚刚开始被理解。在这里,我们使用PKCdelta持续活跃的突变体靶向细胞溶质,细胞核,线粒体和内质网(ER)并检查是否PKCdelta影响其凋亡的亚细胞定位和生存函数。PKCdelta-Cyto、PKCdelta-Mito PKCdelta-Nuc诱导细胞凋亡,而与PKCdelta-ER没有观察到细胞凋亡。PKCdelta-Cyto和PKCdelta-Mito接受乳沟,而没有观察PKCdelta-Nuc和PKCdelta-ER乳沟。同样,caspase-3活动增加细胞overexpressing PKCdelta-Cyto PKCdelta-Mito。与凋亡的影响PKCdelta-Cyto, PKCdelta-Mito, PKCdelta-Nuc, PKCdelta-ER保护细胞免受肿瘤坏死factor-related凋亡诱导ligand-induced etoposide-induced细胞凋亡。此外,过度的PKCdelta kinase-dead突变针对ER废除内生PKCdelta的保护作用,增加肿瘤坏死factor-related凋亡诱导ligand-induced细胞凋亡。的本地化PKCdelta不同影响下游信号通路的激活。 PKCdelta-Cyto increased the phosphorylation of p38 and decreased the phosphorylation of AKT and the expression of X-linked inhibitor of apoptosis protein, whereas PKCdelta-Nuc increased c-Jun NH(2)-terminal kinase phosphorylation. Moreover, p38 phosphorylation and the decrease in X-linked inhibitor of apoptosis protein expression played a role in the apoptotic effect of PKCdelta-Cyto, whereas c-Jun NH(2)-terminal kinase activation mediated the apoptotic effect of PKCdelta-Nuc. Our results indicate that the subcellular localization of PKCdelta plays important roles in its proapoptotic and antiapoptotic functions and in the activation of downstream signaling pathways.