Conventional protein kinase C (PKC)-α and novel PKCε, but not -δ, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts

Abstract A large soluble N-terminal fragment of Alzheimer's disease amyloid precursor protein (secreted form of APP: APP s ) is produced by constitutive processing in the middle of the amyloid β-protein portion of APP. Recent studies indicate that the activation of endogenous protein kinase C (PKC) with phorbol ester raises the rate of secretion of APP s . We constructed rat fibroblast 3Y1 cells that stably overexpress PKC isoenzymes α, δ, or e, and analyzed the amount of APP s released from these PKC transfectants. The levels of APP s released from 3Y1 cells overexpressing PKCα and -e were higher than those from PKCδ-transfected and control cells expressing vector only. These results suggest that specific isoforms of PKC regulate the secretion of APP s through a signaling pathway.