Cited by 201Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingDementia and Cognitive Impairment Research

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In Vitro Phosphorylation of the Cytoplasmic Domain of the Amyloid Precursor Protein by Glycogen Synthase Kinase‐3β

Aplin, Andrew E., Gibb, Graham M., Jacobsen, J. Steven, Gallo, Jean‐Marc, Anderton, Brian H.·1996·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.1996.67020699.x

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Abstract

The two pathological lesions found in the brains of Alzheimer's disease patients, neurofibrillary tangles and neuritic plaques, are likely to be formed through a common pathway. Neurofibrillary tangles are intracellular aggregates of paired helical filaments, the main component of which is hyperphosphorylated forms of the microtubule-associated protein tau. Extracellular neuritic plaques and diffuse and vascular amyloid deposits are aggregates of beta-amyloid protein, a 4-kDa protein derived from the amyloid precursor protein (APP). Using conditions in vitro under which two proline-directed protein kinases, glycogen synthase kinase-3beta (GSK-3beta) and mitogen-activated protein kinase (MAPK), were able to hyperphosphorylate tau, GSK-3beta but not MAPK phosphorylated recombinant APPcyt. The sole site of phosphorylation in APPcyt by GSK-3beta was determined by phosphoamino acid analysis and phosphorylation of APPcyt mutant peptides to be Thr743 (numbering as for APP770). This site was confirmed by endoproteinase Glu-C digestion of APPcyt and peptide sequencing. The ability of GSK-3beta to phosphorylate APPcyt and tau provides a putative link between the two lesions and indicates a critical role of GSK-3beta in the pathogenesis of Alzheimer's disease.

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Crossref · 10.1046/j.1471-4159.1996.67020699.x

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“The phosphorylated residue is Thr668 (numbering for APP695); Cdk5 (Iijima et al., 2000), GSK3 ( Aplin et al., 1996 ), and c-Jun NH2-terminal kinase (JNK; Standen et al., 2001; Muresan and Muresan, 2005a) are the candidate kinases.”
Background
Phosphorylation of Amyloid Precursor Protein at Threonine 668 Is Essential for Its Copper-responsive Trafficking in SH-SY5Y Neuroblastoma Cells
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“APP is phosphorylated at Thr-668 in vitro and in vivo by a number of kinases including glycogen synthase kinase 3 , Jun N-terminal kinase-3 (JNK3), cell division cycle protein (Cdc2), and cyclindependent kinase 5 (Cdk5) (7, 29 –32).”
BackgroundInfluential

Authors: Aplin, A. E., Gibb, G. M., Jacobsen, J. S., Gallo, J., & Anderton, B. H.
Corresponding author: Aplin, Andrew E.
ORCID: Aplin, Andrew E.
Gallo, Jean‐Marc
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 1996-08
Volume: 67
Issue: 2
Pages: 699-707
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.1996.67020699.x
OpenAlex: W2069584842
Cited by: 201
References: 0
Citations by year: 2026: 2 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 13 · 2013: 6 · 2012: 7
FWCI: 1.35
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2305 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: amyloid precursor protein, glycogen synthase kinase-3β, protein phosphorylation, Alzheimer's disease, tau hyperphosphorylation, neurofibrillary tangles, neuritic plaques, amyloid-beta, mitogen-activated protein kinase, phosphorylation site mapping
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cytoplasm, Humans, Molecular Sequence Data, Phosphorylation, Phosphothreonine, Protein-Tyrosine Kinases, Amyloid beta-Protein Precursor, Calcium-Calmodulin-Dependent Protein Kinases, DNA Primers, Mitogen-Activated Protein Kinase 1, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Rats

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In Vitro Phosphorylation of the Cytoplasmic Domain of the Amyloid Precursor Protein by Glycogen Synthase Kinase‐3β

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