Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family.
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.
Köhr
G
G
Centre for Molecular Biology (ZMBH), University of Heidelberg, Heidelberg, Germany.
Seeburg
P H
PH
D002460:Cell Line; D004553:Electric Conductivity; D017353:Gene Deletion; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D019061:src-Family Kinases / Q000502:physiology*
D007473:Ion Channels; D009363:Neoplasm Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; D019061:src-Family Kinases