Postsynaptic Clustering and Activation of Pyk2 by PSD-95
被引:62
作者:
Bartos, Jason A.
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机构:
Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Bartos, Jason A.
[2
]
Ulrich, Jason D.
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Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Ulrich, Jason D.
[2
]
Li, Hongbin
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Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, CanadaUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Li, Hongbin
[3
]
Beazely, Michael A.
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Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, CanadaUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Beazely, Michael A.
[3
]
Chen, Yucui
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Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Chen, Yucui
[2
]
MacDonald, John F.
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Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, CanadaUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
MacDonald, John F.
[3
,4
]
Hell, Johannes W.
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机构:
Univ Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAUniv Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
Hell, Johannes W.
[1
,2
]
机构:
[1] Univ Calif Davis, Dept Pharmacol, Sch Med, Davis, CA 95616 USA
[2] Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[3] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[4] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada
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.