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PMID: 8183935 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 10 ·1994-05-10 ·Pages 4489-93

Buxbaum JD, Ruefli AA, Parker CA, Cypess AM, Greengard P

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.

MeSH Terms
Amyloid beta-Peptides/biosynthesis,isolation & purification Amyloid beta-Protein Precursor/isolation & purification,metabolism Animals CHO Cells Calcium/metabolism Calcium-Transporting ATPases/antagonists & inhibitors Carbachol/pharmacology Cell Line Cricetinae Electrophoresis, Polyacrylamide Gel Glioma Humans Immunoblotting Interleukin-1/pharmacology Models, Biological Molecular Weight Protein Kinase C/metabolism Protein Processing, Post-Translational/drug effects Receptors, Muscarinic/biosynthesis,metabolism Terpenes/pharmacology Thapsigargin Transfection Tumor Cells, Cultured
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor Interleukin-1 Receptors, Muscarinic Terpenes Thapsigargin Carbachol Protein Kinase C Calcium-Transporting ATPases Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Buxbaum J D
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Ruefli A A
Parker C A
Cypess A M
Greengard P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.10.4489
Published
1994-05-10
Pages
4489-93
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43811
Subset
IM
Grants
NIA NIH HHS · AG09464 · United States
NIA NIH HHS · AG10491 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.10.4489 PMC Full Text View journal details
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