Phosphorylation of FE65 Ser610 by serum- and glucocorticoid-induced kinase 1 modulates Alzheimer's disease amyloid precursor protein processing
Copyright policy )Phosphorylation of FE65 Ser610 by serum- and glucocorticoid-induced kinase 1 modulates Alzheimer's disease amyloid precursor protein processing
Alzheimer's disease (AD) is a fatal neurodegenerative disease affecting 36 million people worldwide. Genetic and biochemical research indicate that the excessive generation of amyloid-β peptide (Aβ) from amyloid precursor protein (APP), is a major part of AD pathogenesis. FE65 is a brain-enriched adaptor protein that binds to APP. However, the role of FE65 in APP processing and the mechanisms that regulate binding of FE65 to APP are not fully understood. In the present study, we show that serum- and glucocorticoid-induced kinase 1 (SGK1) phosphorylates FE65 on Ser610 and that this phosphorylation attenuates FE65 binding to APP. We also show that FE65 promotes amyloidogenic processing of APP and that FE65 Ser610 phosphorylation inhibits this effect. Furthermore, we found that the effect of FE65 Ser610 phosphorylation on APP processing is linked to a role of FE65 in metabolic turnover of APP via the proteasome. Thus FE65 influences APP degradation via the proteasome and phosphorylation of FE65 Ser610 by SGK1 regulates binding of FE65 to APP, APP turnover and processing.
- Chinese University of Hong Kong China (People's Republic of)
- King's College London United Kingdom
- Randall Division of Cell and Molecular Biophysics United Kingdom
- Kings College London, University of London United Kingdom
Models, Molecular, 570, Proteasome Endopeptidase Complex, amyloid precursor protein (APP), BETA GENERATION, amyloid-beta peptide, 610, Nerve Tissue Proteins, CHO Cells, HIGH-THROUGHPUT, Immediate-Early Proteins, SIGNALING PATHWAYS, Amyloid beta-Protein Precursor, Cricetulus, Alzheimer Disease, ADAPTER PROTEIN, Chlorocebus aethiops, serum- and glucocorticoid-induced kinase 1 (SGK1), Animals, Aspartic Acid Endopeptidases, Humans, Protein Interaction Domains and Motifs, INTRACELLULAR DOMAIN, APP METABOLISM, DOWN-SYNDROME, Phosphorylation, Research Articles, TRANSGENIC MICE, POSTTRANSLATIONAL MODIFICATIONS, Binding Sites, Nuclear Proteins, Alzheimer's disease, DEGRADATION, HEK293 Cells, FE65, COS Cells, protein degradation, Amyloid Precursor Protein Secretases, Protein Binding
Models, Molecular, 570, Proteasome Endopeptidase Complex, amyloid precursor protein (APP), BETA GENERATION, amyloid-beta peptide, 610, Nerve Tissue Proteins, CHO Cells, HIGH-THROUGHPUT, Immediate-Early Proteins, SIGNALING PATHWAYS, Amyloid beta-Protein Precursor, Cricetulus, Alzheimer Disease, ADAPTER PROTEIN, Chlorocebus aethiops, serum- and glucocorticoid-induced kinase 1 (SGK1), Animals, Aspartic Acid Endopeptidases, Humans, Protein Interaction Domains and Motifs, INTRACELLULAR DOMAIN, APP METABOLISM, DOWN-SYNDROME, Phosphorylation, Research Articles, TRANSGENIC MICE, POSTTRANSLATIONAL MODIFICATIONS, Binding Sites, Nuclear Proteins, Alzheimer's disease, DEGRADATION, HEK293 Cells, FE65, COS Cells, protein degradation, Amyloid Precursor Protein Secretases, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).24 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!