CAKβ/Pyk2 Kinase Is a Signaling Link for Induction of Long-Term Potentiation in CA1 Hippocampus
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Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKbeta/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKbeta/Pyk2, and administering CAKbeta/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKbeta/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKbeta/Pyk2-stimulated enhancement of synaptic AMPA responses was prevented by blocking NMDARS, chelating intracellular Ca(2+), or blocking Src. Thus, activating CAKbeta/Pyk2 is required for inducing LTP and may depend upon downstream activation of Src to upregulate NMDA receptors.
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Pyk2 is involved in long-term potentiation (LTP) through the regulation of Src in an activity-dependent fashion.
“Consistently, Pyk2 was involved in long-term potentiation (LTP) through the regulation of Src in an activity-dependent fashion [57], and in long-term depression (LTD) [55, 109].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [57]
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- Authors
- Huang, Y.-Q., Lu, W.-Y., Ali, D. W., Pelkey, K. A., Pitcher, G. M., Lu, Y. M., Aoto, H., Roder, J. C., Sasaki, T., Salter, M. W., & MacDonald, J. F.
- Affiliations
- University of Toronto (CA)
- Mount Sinai Hospital (CA)
- Sapporo Medical University (JP)
- Corresponding author
- Salter, Michael W
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 29
- Issue
- 2
- Pages
- 485-496
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2122643181
- Cited by
- 274
- References
- 1
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 8 · 2023: 6 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 6 · 2018: 14 · 2017: 9 · 2016: 3 · 2015: 10 · 2014: 12 · 2013: 12 · 2012: 12
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) (submittedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Ontario Neurotrauma Foundation
- Hospital for Sick Children
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- long-term potentiation, focal adhesion kinase, Pyk2, Src family kinases, NMDA receptor, hippocampal CA1, synaptic plasticity, tyrosine phosphorylation, AMPA receptors, intracellular calcium, learning and memory
- MeSH terms
- Animals, Hippocampus, Male, Protein-Tyrosine Kinases, Signal Transduction, Up-Regulation, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Pyramidal Cells, Receptors, AMPA, src-Family Kinases, Rats, Focal Adhesion Kinase 2
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