Journal
JOURNAL OF NEUROCHEMISTRY
Volume 75, Issue 3, Pages 1085-1091Publisher
WILEY
DOI: 10.1046/j.1471-4159.2000.0751085.x
Keywords
Alzheimer's beta-amyloid precursor protein; Alzheimer's disease; cyclin-dependent kinase 5; protein phosphorylation
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Funding
- NATIONAL INSTITUTE ON AGING [P01AG009464] Funding Source: NIH RePORTER
- NIA NIH HHS [AG09464] Funding Source: Medline
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The mature form of Alzheimer's P-amyloid precursor protein (APP) is phosphorylated specifically at Thr(668) in neurons. In mature neurons, phosphorylated APP is detected in neurites, with dephosphorylated APP being found mostly in the cell body. In vitro, active cyclin-dependent kinase 5 (Cdk5) phosphorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature neurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and significantly diminished the level of phosphorylated APP, The expression of APP was unaffected in antisense-treated neurons. These results indicate that in neurons APP is phosphorylated by Cdk5, and that this may play a role in its localization.
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