Postsynaptic clustering and activation of Pyk2 by PSD-95

Jason A. Bartos, Jason D. Ulrich, Hongbin Li, Michael A. Beazely, Yucui Chen, John F. MacDonald, Johannes W Hell

Research output: Contribution to journalArticle

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Abstract

The tyrosine kinase Pyk2 plays a unique role in intracellular signal transduction by linking Ca2+ influx to tyrosine phosphorylation, but the molecular mechanism of Pyk2 activation is unknown. We report that Pyk2 oligomerization by antibodies in vitro or overexpression of PSD-95 in PC6-3 cells induces trans-autophosphorylation of Tyr402, the first step in Pyk2 activation. In neurons, Ca2+ influx through NMDA-type glutamate receptors causes postsynaptic clustering and autophosphorylation of endogenous Pyk2 via Ca2+- and calmodulin-stimulated binding to PSD-95. Accordingly, Ca2+ influx promotes oligomerization and thereby autoactivation of Pyk2 by stimulating its interaction with PSD-95. We show that this mechanism of Pyk2 activation is critical for long-term potentiation in the hippocampus CA1 region, which is thought to underlie learning and memory.

Original languageEnglish (US)
Pages (from-to)449-463
Number of pages15
JournalJournal of Neuroscience
Volume30
Issue number2
DOIs
StatePublished - Jan 13 2010

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Long-Term Potentiation
Glutamate Receptors
Calmodulin
N-Methyl-D-Aspartate Receptors
Protein-Tyrosine Kinases
Cluster Analysis
Tyrosine
Signal Transduction
Hippocampus
Phosphorylation
Learning
Neurons
Antibodies
In Vitro Techniques
PC6 extract

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bartos, J. A., Ulrich, J. D., Li, H., Beazely, M. A., Chen, Y., MacDonald, J. F., & Hell, J. W. (2010). Postsynaptic clustering and activation of Pyk2 by PSD-95. Journal of Neuroscience, 30(2), 449-463. https://doi.org/10.1523/JNEUROSCI.4992-08.2010

Postsynaptic clustering and activation of Pyk2 by PSD-95. / Bartos, Jason A.; Ulrich, Jason D.; Li, Hongbin; Beazely, Michael A.; Chen, Yucui; MacDonald, John F.; Hell, Johannes W.

In: Journal of Neuroscience, Vol. 30, No. 2, 13.01.2010, p. 449-463.

Research output: Contribution to journalArticle

Bartos, JA, Ulrich, JD, Li, H, Beazely, MA, Chen, Y, MacDonald, JF & Hell, JW 2010, 'Postsynaptic clustering and activation of Pyk2 by PSD-95', Journal of Neuroscience, vol. 30, no. 2, pp. 449-463. https://doi.org/10.1523/JNEUROSCI.4992-08.2010
Bartos JA, Ulrich JD, Li H, Beazely MA, Chen Y, MacDonald JF et al. Postsynaptic clustering and activation of Pyk2 by PSD-95. Journal of Neuroscience. 2010 Jan 13;30(2):449-463. https://doi.org/10.1523/JNEUROSCI.4992-08.2010
Bartos, Jason A. ; Ulrich, Jason D. ; Li, Hongbin ; Beazely, Michael A. ; Chen, Yucui ; MacDonald, John F. ; Hell, Johannes W. / Postsynaptic clustering and activation of Pyk2 by PSD-95. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 2. pp. 449-463.
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