CONVENTIONAL PROTEIN-KINASE-C (PKC)-ALPHA AND NOVEL PKC-EPSILON, BUT NOT PKC-DELTA, INCREASE THE SECRETION OF AN N-TERMINAL FRAGMENT OF ALZHEIMERS-DISEASE AMYLOID PRECURSOR PROTEIN FROM PKC CDNA TRANSFECTED 3Y1 FIBROBLASTS

A large soluble N-terminal fragment of Alzheimer's disease amyloid pre cursor protein (secreted form of APP: APP(s)) is produced by constitut ive processing in the middle of the amyloid beta-protein portion of AP P. Recent studies indicate that the activation of endogenous protein k inase C (PKC) with phorbol ester raises the rate of secretion of APP(s ). We constructed rat fibroblast 3Y1 cells that stably overexpress PKC isoenzymes alpha, delta, or epsilon, and analyzed the amount of APP(s ) released from these PKC transfectants, The levels of APP(s) released from 3Y1 cells overexpressing PKC alpha and -epsilon were higher than those from PKC delta-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.