Effect of increased glycogen synthase kinase-3 activity upon the maturation of the amyloid precursor protein in transfected cells.

Aberrant control of protein phosphorylation is an important feature in Alzheimer's disease pathology. The action of glycogen synthase kinase-3 beta (GSK-3 beta) on the maturation and phosphorylation of an amyloid precursor protein-reporter construct (APP-REP) was studied in transfected COS-7 cells. Elevation of GSK-3 beta activity by enzyme over-expression resulted in an increase in the level of mature forms of co-expressed APP-REP. This effect was not associated with an increased level of APP-REP phosphorylation at Thr743, an in vitro GSK-3 beta phosphorylation site. These findings suggest that GSK-3 beta activity may indirectly increase cellular maturation of APP, which may subsequently result in altered production of beta-amyloid protein.