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Cited by 55Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsTreatment of Major Depression

Proline-Rich Tyrosine Kinase 2 Regulates Hippocampal Long-Term Depression

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Hsin, Honor, Kim, Myung Jong, Wang, Chi-Fong, Sheng, Morgan·2010·The Journal of Neuroscience
DOI 10.1523/jneurosci.1029-10.2010PMC PMC4122232
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Abstract

Proline-rich tyrosine kinase 2 (PYK2), also known as cell adhesion kinase β or protein tyrosine kinase 2b, is a calcium-dependent signaling protein involved in cell migration. Phosphorylation of residue Y402 is associated with activation of PYK2 and leads to the recruitment of downstream signaling molecules. PYK2 was previously implicated in long-term potentiation (LTP); however, the role of PYK2 in long-term depression (LTD) is unknown. Here, we report that PYK2 is activated by NMDA receptor stimulation (chemical LTD) in cultured neurons. Small hairpin RNA-mediated knockdown of PYK2 blocks LTD, but not LTP, in hippocampal slice cultures. We find that the Y402 residue and, to a lesser extent, PYK2 kinase activity contribute to PYK2's role in LTD. Knockdown experiments indicate that PYK2 is required to suppress NMDA-induced extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of PYK2 depresses NMDA-induced ERK phosphorylation and inhibits LTP, but not LTD. Our data indicate that PYK2 is critical for the induction of LTD, possibly in part by antagonizing ERK signaling in hippocampal neurons.

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Authors
Hsin, H., Kim, M. J., Wang, C.-F., & Sheng, M.
Affiliations
Massachusetts Institute of Technology (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2010-09-08
Volume
30
Issue
36
Pages
11983-11993
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.1029-10.2010
PMC
PMC4122232
OpenAlex
W2088260648
Cited by
55
References
7
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 8 · 2018: 7 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 8
FWCI
1.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
National Institute of General Medical Sciences (T32GM007753)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
Pyk2, long-term depression, long-term potentiation, hippocampus, NMDA receptor, ERK1/2 phosphorylation, calcium-dependent signaling, synaptic plasticity
MeSH terms
Analysis of Variance, Animals, Animals, Newborn, Biophysics, Cell Line, Transformed, Electric Stimulation, Hippocampus, Humans, Immunosuppressive Agents, Lysine, Organ Culture Techniques, Phosphorylation, Serine, Transfection, Receptors, N-Methyl-D-Aspartate, Tacrolimus, Receptors, AMPA, RNA Interference, Long-Term Synaptic Depression, Green Fluorescent Proteins, Rats, Focal Adhesion Kinase 2

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