Cell Cycle-Dependent Regulation of the Phosphorylation and Metabolism of the Alzheimer Amyloid Precursor Protein

Suzuki, T., Oishi, M., Marshak, D. R., Czernik, A. J., Nairn, A. C., Greengard, P. (March 1994) Cell Cycle-Dependent Regulation of the Phosphorylation and Metabolism of the Alzheimer Amyloid Precursor Protein. Embo Journal, 13 (5). pp. 1114-1122. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/8131745

Abstract

Accumulation of the amyloid A beta peptide, which is derived from a larger precursor protein (APP), and the formation of plaques, are major events believed to be involved in the etiology of Alzheimer's disease. Abnormal regulation of the metabolism of APP may contribute to the deposition of plaques. APP is an integral membrane protein containing several putative phosphorylation sites within its cytoplasmic domain. We report here that APP is phosphorylated at Thr668 by p34(cdc2) protein kinase (cdc2 kinase) in vitro, and in a cell cycle-dependent manner in vivo. At the G(2)/M phase of the cell cycle, when APP phosphorylation is maximal, the levels of mature APP (mAPP) and immature APP (imAPP) do not change significantly. However, imAPP is altered qualitatively. Furthermore, the level of the secreted extracellular N-terminal domain (APP(S)) is decreased and that of the truncated intracellular C-terminal fragment (APP(COOH)) is increased. These findings suggest the possibility that phosphorylation-dependent events occurring during the cell cycle affect the metabolism of APP. Alterations in these events might play a role in the pathogenesis of Alzheimer's disease.

Item Type: Paper
Uncontrolled Keywords: ALZHEIMERS DISEASE AMYLOID PRECURSOR PROTEIN CELL CYCLE P34(CDC2) PROTEIN KINASE PROTEIN PHOSPHORYLATION CASEIN KINASE-II BETA-PEPTIDE TAU-PROTEIN DISEASE CDC2 CDNA PHOSPHOPROTEIN DERIVATIVES SECRETION CLEAVAGE
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > organs types and functions > metabolism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: March 1994
Date Deposited: 08 May 2015 16:52
Last Modified: 08 May 2015 16:52
PMCID: PMC394920
URI: http://repository.cshl.edu/id/eprint/31460

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