Alt Addy, Gartsbein Marina, Ohba Motoi, Kuroki Toshio, Tennenbaum Tamar
Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Biochem Biophys Res Commun. 2004 Jan 30;314(1):17-23. doi: 10.1016/j.bbrc.2003.12.053.
In mammalian epidermis, alpha6beta4 integrin is expressed exclusively on the basal layer localized to the hemidesmosomes, where it interacts extracellularly with the laminin-5 ligand. During differentiation, loss of alpha6beta4 is associated with keratinocyte detachment from the basement membrane and upward migration. The protein kinase C (PKC) family of isoforms participates in regulation of integrin function and is linked to skin differentiation. Exposure of primary murine keratinocytes to PKC activators specifically downregulates alpha6beta4 expression. Utilizing recombinant adenoviruses, we selectively overexpressed skin PKC isoforms in primary keratinocytes. PKCdelta and PKCzeta induced downregulation of alpha6beta4 protein expression, leading to reduced keratinocyte attachment to laminin-5 and enhanced gradual detachment from the underlying matrix. In contrast, PKCalpha upregulated alpha6beta4 protein expression, leading to increased keratinocyte attachment to laminin-5 and to the underlying matrix. Altogether, these results suggest distinct roles for specific PKC isoforms in alpha6beta4 functional regulation during the early stages of skin differentiation.
在哺乳动物表皮中，α6β4整合素仅在位于半桥粒的基底层表达，在那里它在细胞外与层粘连蛋白-5配体相互作用。在分化过程中，α6β4的缺失与角质形成细胞从基底膜脱离并向上迁移有关。蛋白激酶C（PKC）同工型家族参与整合素功能的调节，并与皮肤分化相关。将原代小鼠角质形成细胞暴露于PKC激活剂会特异性地下调α6β4的表达。利用重组腺病毒，我们在原代角质形成细胞中选择性地过表达皮肤PKC同工型。PKCδ和PKCζ诱导α6β4蛋白表达下调，导致角质形成细胞与层粘连蛋白-5的附着减少，并增强了从下层基质的逐渐脱离。相反，PKCα上调α6β4蛋白表达，导致角质形成细胞与层粘连蛋白-5和下层基质的附着增加。总之，这些结果表明特定的PKC同工型在皮肤分化早期α6β4功能调节中具有不同的作用。
