NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src
@article{Yu1997NMDACR, title={NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src}, author={X M Yu and Rand Askalan and G J Keil and Michael W. Salter}, journal={Science}, year={1997}, volume={275}, pages={674 - 678} }
The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and plasticity in the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In membrane patches excised from mammalian central neurons, the endogenous tyrosine kinase Src was shown to regulate the activity of NMDA channels. The action of Src required a sequence [Src(40–58)] within the noncatalytic, unique domain of Src. In addition, Src coprecipitated with NMDA receptor proteins. Finally, endogenous Src…
622 Citations
G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors
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G-protein-coupled receptors can regulate NMDA receptor function indirectly through a PKC-dependent activation of the non-receptor tyrosine kinase (Src) signaling cascade.
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In the central nervous system, synaptic strength is regulated partly by changes in the function and number of postsynaptic glutamate receptors, and members of the Src family of protein tyrosine kinases upregulate NMDAR function, thereby gating the production of N MDAR-dependent synaptic potentiation.
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It is demonstrated that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells, suggesting that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
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It is found that RACK1 binds both the NR2B subunit of the NMDA receptor and the nonreceptor protein tyrosine kinase, Fyn and may play a role in synaptic plasticity, addiction, learning, and memory.
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- BiologyNature Neuroscience
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Post-synaptic density-93 mediates tyrosine-phosphorylation of the N-methyl-d-aspartate receptors
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- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1999
It is proposed that the boost in NMDA receptor function produced by the coincidence of activating Src and raising intracellular sodium may be important in physiological and pathophysiological enhancement of excitatory transmission in the dorsal horn of the spinal cord and elsewhere in the central nervous system.
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