Department of Cellular Signaling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
FEBS Lett. 2011 Apr 20;585(8):1243-8. doi: 10.1016/j.febslet.2011.03.058. Epub 2011 Mar 30.
The aim of the present study was to analyse the alterations of cyclin dependent kinase 5 (Cdk5) expression and phosphorylation in PC12 cells overexpressing amyloid precursor protein (APP). Our results demonstrated enhanced cell death and increased levels of mRNA for the Cdk5 gene in APP-transfected cells. Significantly decreased phosphorylation of Cdk5 at Tyr15 was observed in APPsw cells, which is responsible for a reduction in Cdk5 activity. Cdk5-dependent phosphorylation of glycogen synthase kinase-3β (Gsk-3β) at Ser9 was also decreased, which can lead to the increase of Gsk-3β activity and hyperphosphorylation of MAP tau. Our results demonstrate for the first time, a deregulation of Cdk5 phosphorylation in APP-transfected cells.
本研究旨在分析过表达淀粉样前体蛋白 (APP) 的 PC12 细胞中细胞周期蛋白依赖性激酶 5 (Cdk5) 表达和磷酸化的变化。我们的结果表明，APP 转染细胞的细胞死亡增加，Cdk5 基因的 mRNA 水平升高。在 APPsw 细胞中观察到 Cdk5 的 Tyr15 磷酸化显著减少，这导致 Cdk5 活性降低。Cdk5 依赖性糖原合酶激酶-3β (Gsk-3β) 在 Ser9 的磷酸化也减少，这可能导致 Gsk-3β 活性增加和 MAP tau 的过度磷酸化。我们的结果首次证明了 APP 转染细胞中 Cdk5 磷酸化的失调。
