Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family

J Physiol. 1996 Apr 15;492 ( Pt 2)(Pt 2):445-52. doi: 10.1113/jphysiol.1996.sp021320.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Electric Conductivity
  • Gene Deletion
  • Humans
  • Ion Channels / metabolism*
  • Neoplasm Proteins*
  • Protein-Tyrosine Kinases / physiology
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Recombinant Proteins
  • src-Family Kinases / physiology*


  • Ion Channels
  • Neoplasm Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Protein-Tyrosine Kinases
  • FRK protein, human
  • src-Family Kinases