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Cell cycle‐dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein.
Author(s) -
Suzuki T.,
Oishi M.,
Marshak D.R.,
Czernik A.J.,
Nairn A.C.,
Greengard P.
Publication year - 1994
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1994.tb06360.x
Subject(s) - biology , phosphorylation , metabolism , microbiology and biotechnology , amyloid (mycology) , cell cycle , biochemistry , amyloid precursor protein , alzheimer's disease , cell , disease , medicine , botany
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 p34cdc2 protein kinase (cdc2 kinase) in vitro, and in a cell cycle‐dependent manner in vivo. At the G2/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 (APPS) is decreased and that of the truncated intracellular C‐terminal fragment (APPCOOH) 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.