Lippincott Williams & Wilkins, Inc., Philadelphia
Neuron-Specific Phosphorylation of Alzheimer's β-Amyloid Precursor Protein by Cyclin-Dependent Kinase 5
Article first published online: 4 JAN 2002
Journal of Neurochemistry
Volume 75, Issue 3, pages 1085–1091, September 2000
How to Cite
Iijima, K.-i., Ando, K., Takeda, S., Satoh, Y., Seki, T., Itohara, S., Greengard, P., Kirino, Y., Nairn, A. C. and Suzuki, T. (2000), Neuron-Specific Phosphorylation of Alzheimer's β-Amyloid Precursor Protein by Cyclin-Dependent Kinase 5. Journal of Neurochemistry, 75: 1085–1091. doi: 10.1046/j.1471-4159.2000.0751085.x
Abbreviations used: AD, Alzheimer's disease; APLP2, amyloid precursor-like protein 2; APP, Alzheimer's β-amyloid precursor protein; Cdk5, cyclin-dependent kinase 5; FITC, fluorescein isothiocyanate; GSK3β, glycogen synthase kinase-3β; GST, glutathione S-transferase; imAPP, immature APP; mAPP, mature APP; PAGE, polyacrylamide gel electrophoresis; PiAPP, phosphorylated APP; SDS, sodium dodecyl sulfate; TRITC, tetramethylrhodamine B isothiocyanate.
- Issue published online: 4 JAN 2002
- Article first published online: 4 JAN 2002
- Alzheimer's β-amyloid precursor protein;
- Alzheimer's disease;
- Cyclin-dependent kinase 5;
- Protein phosphorylation
Abstract: The mature form of Alzheimer's β-amyloid precursor protein (APP) is phosphorylated specifically at Thr668 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 Thr668. 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.