Phosphorylation of FE65 at threonine 579 by GSK3β stimulates amyloid precursor protein processing
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AbstractExcessive generation of amyloid-β peptide (Aβ) by aberrant proteolysis of amyloid precursor protein (APP) is a key event in Alzheimer's disease (AD) pathogenesis. FE65 is a brain-enriched phospho-adaptor protein that interacts with APP and has been shown to modulate APP processing. However, the mechanism(s) that FE65 alters APP processing is still not fully understood. In the present study, we demonstrate that FE65 is phosphorylated at threonine 579 (T579) by glycogen synthase kinase 3β (GSK3β). Moreover, FE65 T579 phosphorylation potentiates γ- and β-secretases-mediated APP processing and Aβ liberation. Additionally, the phosphorylation suppresses FE65 PTB2 intermolecular dimerization but enhances FE65/APP complex formation. Hence, our findings reveal a novel mechanism that GSK3β stimulates amyloidogenic processing of APP by phosphorylation of FE65 at T579.
Acceptance Date06/09/2017
All Author(s) ListYat Shing Lee, Wan Ning Vanessa Chow, Kwok-Fai Lau
Journal nameScientific Reports
Volume Number7
Place of PublicationUK
Article number12456
LanguagesEnglish-United Kingdom
KeywordsFE65, GSK3β, phosphorylation, APP, Aβ

Last updated on 2020-01-07 at 03:09