AMYLOID PRECURSOR PROTEIN IS NOT PROCESSED BY FURIN, PACE-4, PC1 3, PC2, PC4 AND PC5/6 OF THE FURIN FAMILY OF PROPROTEIN PROCESSING ENZYMES/

Proteolytic cleavage of the amyloid precursor protein (APP) has previo usly been shown to release its extracellular domain into the medium. T he identification of the responsible proteinase(s), termed secretase(s ), is a high priority in ongoing Alzheimer research. This is hampered by the unusual characteristics of these enzyme(s) and by the fact that they cleave only membrane associated APP. We report here, using a vac cinia virus based expression system, that pig kidney PK(15) cells expr ess full-length, membrane bound APP695, but that secretion of APP is l ow. This heterologous expression system allows to assay candidate secr etases in a cellular context by simple co-transfection of the APP and candidate secretase cDNA containing plasmids. Eight different members of the mouse and human furin family of proprotein processing enzymes w ere tested in this assay, but none of them enhanced the secretion of A PP. Secretion of von Willebrand's factor was used as a positive contro l.