Phosphorylation of FE65 at threonine 579 by GSK3β stimulates amyloid precursor protein processing.
Yat Shing Lee, Wan Ning Vanessa Chow, Kwok-Fai Lau
Author Information
Yat Shing Lee: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR.
Wan Ning Vanessa Chow: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR.
Kwok-Fai Lau: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR. kflau@cuhk.edu.hk.
Excessive 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.
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Amyloid beta-Protein Precursor
Animals
Base Sequence
CHO Cells
COS Cells
Chlorocebus aethiops
Cricetulus
Genes, Reporter
Glycogen Synthase Kinase 3 beta
HEK293 Cells
Humans
Luciferases
Nerve Tissue Proteins
Nuclear Proteins
Phosphorylation
Plasmids
Protein Binding
Protein Processing, Post-Translational
Sequence Alignment
Sequence Homology, Nucleic Acid
Threonine
Transfection
APBB1 protein, human
APP protein, human
Amyloid beta-Protein Precursor
Nerve Tissue Proteins
Nuclear Proteins
Threonine
Luciferases
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
