METABOLISM OF ALZHEIMER BETA-AMYLOID PRECURSOR PROTEIN - REGULATION BY PROTEIN-KINASE-A IN INTACT-CELLS AND IN A CELL-FREE SYSTEM

Various compounds that affect signal transduction regulate the relativ e utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the productio n of nonamyloidogenic soluble beta APP (s beta APP) and decreasing tha t of amyloidogenic beta-amyloid peptide. In a recent study directed to ward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forsk olin increases s beta APP production from intact PC12 cells, and prote in kinase A stimulates formation from the TGN of beta APP-containing v esicles. Although protein kinase A and protein kinase C converge at th e level of formation from the TGN of beta APP-containing vesicles, add itional evidence indicates that the regulatory mechanisms involved are distinct.