title: Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner.
abstract: Various first messengers linked to phospholipase C, including acetylcholine and interleukin 1, regulate the production both of the secreted form of the amyloid protein precursor (APP) and of amyloid beta-protein. We have now identified intracellular signals which are responsible for mediating these effects. We show that activation of phospholipase C may affect APP processing by either of two pathways, one involving an increase in protein kinase C and the other an increase in cytoplasmic calcium levels. The effects of calcium on APP processing appear to be independent of protein kinase C activation. The observed effects of calcium on APP processing may be of therapeutic utility.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: A A
authors.initials: AA
authors.lastname: Ruefli
authors.forename: C A
authors.initials: CA
authors.lastname: Parker
authors.forename: A M
authors.initials: AM
authors.lastname: Cypess
authors.forename: P
authors.initials: P
authors.lastname: Greengard
mesh_terms: D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000302:isolation & purification; D016564:Amyloid beta-Protein Precursor / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D005910:Glioma; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000494:pharmacology; D008954:Models, Biological; D008970:Molecular Weight; D011493:Protein Kinase C / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D011976:Receptors, Muscarinic; D013729:Terpenes; D019284:Thapsigargin; D002217:Carbachol; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D002118:Calcium