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 journalArticlepeer-review

63 Scopus citations


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
Issue number2
StatePublished - Jan 13 2010
Externally publishedYes


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