CAK beta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus

Citation
Yq. Huang et al., CAK beta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus, NEURON, 29(2), 2001, pp. 485-496
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEURON
ISSN journal
0896-6273 → ACNP
Volume
29
Issue
2
Year of publication
2001
Pages
485 - 496
Database
ISI
SICI code
0896-6273(200102)29:2<485:CBKIAS>2.0.ZU;2-T
Abstract
Long-term potentiation (LTP) is an activity-dependent enhancement of synapt ic efficacy, considered a model of learning and memory. The biochemical cas cade producing LTP requires activation of Src, which upregulates the functi on of NMDA receptors (NMDARs), but how Src becomes activated is unknown. He re, we show that the focal adhesion kinase CAK beta /Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP wa s prevented by blocking CAK beta /Pyk2, and administering CAK beta /Pyk2 in tracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAK be ta /Pyk2 and its association with Src was increased by stimulation that pro duced LTP. Finally, CAK beta /Pyk2-stimulated enhancement of synaptic AMPA responses was prevented by blocking NMDARS, chelating intracellular Ca2+, o r blocking Src. Thus, activating CAK beta /Pyk2 is required for inducing LT P and may depend upon downstream activation of Src to upregulate NMDA recep tors.