Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family
- PMID: 9019541
- PMCID: PMC1158839
- DOI: 10.1113/jphysiol.1996.sp021320
Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family
Abstract
1. Tyrosine kinases regulate NMDA receptor-channel activity in cultured neurons, and NMDA receptor subunits are tyrosine phosphorylated in the brain. 2. Heteromeric NMDA receptor-channels were transiently expressed in human embryonic kidney (HEK) 293 cells and glutamate (100 microM)-activated whole-cell currents (500 ms) were studied when tyrosine kinases of the src gene family were included in the pipette solution. 3. Glutamate-activated currents (evoked every 20 s for up to 20 min) were increased by src and fyn kinases without affecting the desensitization and deactivation kinetics in NR1-NR2A but the kinases had no effects in NR1-NR2B, NR1-NR2C and NR1-NR2D receptor-channels, suggesting that a phosphorylation site in NR2A is targeted. 4. In a mutant channel consisting of NR1 and a C-terminal deletion mutant of NR2A (NR2A delta C), src and fyn kinases lost their potentiating effects indicating that the phosphorylation of tyrosine(s) in the C-terminal domain of NR2A affects the current flux through native NMDA receptor-channels.
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