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首页> 外文期刊>Molecular and Cellular Biology >Induction of Differentiation in Normal Human Keratinocytes by Adenovirus-Mediated Introduction of the η and δ Isoforms of Protein Kinase C
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Induction of Differentiation in Normal Human Keratinocytes by Adenovirus-Mediated Introduction of the η and δ Isoforms of Protein Kinase C

机译：腺病毒介导的蛋白激酶C的η和δ同工型诱导正常人角质形成细胞的分化

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Protein kinase C (PKC) plays a crucial role(s) in regulation of growth and differentiation of cells. In the present study, we examined possible roles of the α, δ, η, and ζ isoforms of PKC in squamous differentiation by overexpressing these genes in normal human keratinocytes. Because of the difficulty of introducing foreign genes into keratinocytes, we used an adenovirus vector system, Ax, which allows expression of these genes at a high level in almost all the cells infected for at least 72 h. Increased kinase activity was demonstrated in the cells overexpressing the α, δ, and η isoforms. Overexpression of the η isoform inhibited the growth of keratinocytes of humans and mice in a dose (multiplicity of infection [MOI])-dependent manner, leading to G1 arrest. The η-overexpressing cells became enlarged and flattened, showing squamous cell phenotypes. Expression and activity of transglutaminase 1, a key enzyme of squamous cell differentiation, were induced in the η-overexpressing cells in dose (MOI)- and time-dependent manners. The inhibition of growth and the induction of transglutaminase 1 activity were found only in the cells that express the η isoform endogenously, i.e., in human and mouse keratinocytes but not in human and mouse fibroblasts or COS1 cells. A dominant-negative η isoform counteracted the induction of transglutaminase 1 by differentiation inducers such as a phorbol ester, 1α,25-dihydroxyvitamin D3, and a high concentration of Ca2+. Among the isoforms examined, the δ isoform also inhibited the growth of keratinocytes and induced transglutaminase 1, but the α and ζ isoforms did not. These findings indicate that the η and δ isoforms of PKC are involved crucially in squamous cell differentiation.
机译：蛋白激酶C（PKC）在调节细胞的生长和分化中起着至关重要的作用。在本研究中，我们通过在正常人角质形成细胞中过表达这些基因，研究了PKC的α，δ，η和ζ亚型在鳞状细胞分化中的可能作用。由于难以将外源基因导入角质形成细胞，我们使用了腺病毒载体系统Ax，该系统可在至少72 h的几乎所有细胞中高水平表达这些基因。在过表达α，δ和η同工型的细胞中证实了激酶活性的增加。 η亚型的过度表达以剂量（感染复数[MOI]）依赖性方式抑制人和小鼠角质形成细胞的生长，导致G 1 阻滞。过量表达η的细胞变大并变平，显示出鳞状细胞表型。转谷氨酰胺酶1（一种鳞状细胞分化的关键酶）的表达和活性以剂量（MOI）和时间依赖性方式在η过表达的细胞中诱导。仅在内源表达η同工型的细胞中，即在人和小鼠角质形成细胞中发现生长抑制和转谷氨酰胺酶1活性的诱导，而在人和小鼠成纤维细胞或COS1细胞中没有发现。显性负η型亚型通过佛波酯，1α，25-二羟基维生素D 3 和高浓度Ca 2 + 。在检查的同工型中，δ同工型还抑制了角质形成细胞的生长并诱导了转谷氨酰胺酶1，但α和ζ同工型却没有。这些发现表明，PKC的η和δ同工型与鳞状细胞分化至关重要。

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