Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation
| Autor: | P Cicchetti, A J Unterbeck, Andrew J. Czernik, Michelle Ehrlich, Joseph D. Buxbaum, T. V. Ramabhadran, Sam Gandy, Paul Greengard, R P Fracasso |
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| Rok vydání: | 1990 |
| Předmět: |
Amyloid
Transcription Genetic Adrenal Gland Neoplasms Pheochromocytoma Cell Line Amyloid beta-Protein Precursor chemistry.chemical_compound Methionine Alzheimer Disease Ethers Cyclic Okadaic Acid Amyloid precursor protein Animals Humans Protein phosphorylation Phosphorylation Protein Precursors Phorbol 12 13-Dibutyrate Protein Kinase C Protein kinase C Multidisciplinary biology Okadaic acid Biochemistry of Alzheimer's disease Molecular Weight Kinetics chemistry Biochemistry Alpha secretase Protein Biosynthesis Phorbol biology.protein Tetradecanoylphorbol Acetate Protein Processing Post-Translational Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 87:6003-6006 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The turnover and processing of the Alzheimer beta/A4 amyloid precursor protein (beta APP) has been studied in PC12 cells after treatment with agents that regulate protein phosphorylation. Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the levels of 15- and 19-kDa peptides. These peptides appeared to be COOH-terminal fragments of beta APP, which arose when phorbol 12,13-dibutyrate increased the rate of proteolytic processing of mature forms of beta APP. Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, also led to decreased levels of mature beta APP and increased levels of the 15- and 19-kDa peptides. H-7, an inhibitor of protein kinase C and of several other protein kinases, apparently decreased the rate of proteolytic processing of mature beta APP. The sizes of the putative COOH-terminal fragments observed after treatment with either phorbol 12,13-dibutyrate or okadaic acid suggest that one or both may contain the entire beta/A4 region of beta APP and thus be amyloidogenic. Our results support the hypothesis that abnormal protein phosphorylation may play a role in the development of the cerebral amyloidosis that accompanies Alzheimer disease. |
| Databáze: | OpenAIRE |
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