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Proline-Rich Tyrosine Kinase 2 Regulates Hippocampal Long-Term Depression
Name
11983.full.pdf
Description
Published version
Size
1.97 MB
Format
Adobe PDF
Checksum (MD5)
701bced0020d61dd306cc4f49b35f298
Author(s)
Hsin, H
Kim, MJ
Wang, C-F
Sheng, M
Date Issued
2010
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Hsin, H., et al. "Proline-Rich Tyrosine Kinase 2 Regulates Hippocampal Long-Term Depression." Journal of Neuroscience 30 36 (2010): 11983-93.
Version
Final published version
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. Copyright © 2010 the authors.
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1523/JNEUROSCI.1029-10.2010
