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Cited by 52Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchProtein Kinase Regulation and GTPase Signaling

Pyk2 is a Novel Tau Tyrosine Kinase that is Regulated by the Tyrosine Kinase Fyn

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Li, Chuanzhou, Götz, Jürgen·2018·Journal of Alzheimer’s Disease
DOI 10.3233/jad-180054PMC PMC6004899
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Abstract

The protein tyrosine kinase Pyk2 is encoded by PTK2B, a novel Alzheimer’s disease (AD) susceptibility variant, with the PTK2B risk allele being associated with increased mRNA levels, suggestive of increased Pyk2 levels. However, the role of Pyk2, a member of the focal adhesion kinase (FAK) family, in AD pathology and its regulation are largely unknown. To address this, we generated mice with neuronal expression of human Pyk2. Because we had previously reported an association of Pyk2 and hyperphosphorylated tau (a hallmark feature of AD) in human tau transgenic pR5 mice, we also generated Pyk2/tau double-transgenic mice, which exhibit increased tyrosine phosphorylation and accumulation of tau. We further demonstrated that Pyk2 colocalizes, interacts with, and phosphorylates tau in vivo and in vitro. Importantly, although Pyk2 interacts with the established tyrosine-directed tau kinase Fyn, we identified an increased Pyk2 activity in mice which constitutively overexpress Fyn (FynCA), and a decreased activity in mice lacking Fyn (FynKO). Together, our study reveals a novel role for Pyk2 as a direct tyrosine kinase of tau that is active downstream of Fyn. Our analysis may enhance the understanding of how the PTK2B risk allele contributes to tauopathy.

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Authors
Li, C., & Götz, J.
Affiliations
The University of Queensland (AU)
Corresponding author
Götz, Jürgen
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2018-05-16
Volume
64
Issue
1
Pages
205-221
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-180054
PMC
PMC6004899
OpenAlex
W2804757593
Cited by
52
References
4
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 6 · 2019: 7 · 2018: 3
FWCI
4.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Australian Government (ACT900116)
  • Medical Research Council
  • Australian Research Council (LE130100078, DP160103812)
  • National Health and Medical Research Council (1127999, 1037746)
  • Caring for our Country
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
Pyk2
MeSH terms
Disks Large Homolog 4 Protein, Adenosine Triphosphate, Animals, Disease Models, Animal, Gene Expression Regulation, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Mutation, Phosphorylation, RNA, Messenger, Transfection, tau Proteins, Tauopathies, Proto-Oncogene Proteins c-fyn, Mice, Focal Adhesion Kinase 2, HEK293 Cells

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