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 relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward 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 forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.
Xu
H
H
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
Sweeney
D
D
Greengard
P
P
Gandy
S
S
D000544:Alzheimer Disease / Q000628:therapy; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002474:Cell-Free System; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019319:Okadaic Acid; D016716:PC12 Cells; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D005576:Colforsin; D019319:Okadaic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C