Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner.
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.
Buxbaum
J D
JD
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Ruefli
A A
AA
Parker
C A
CA
Cypess
A M
AM
Greengard
P
P
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
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