Alterations of cyclin dependent kinase 5 expression and phosphorylation in amyloid precursor protein (APP)-transfected PC12 cells.

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.