Premium
Subtype‐specific regulation of recombinant NMDA receptor‐channels by protein tyrosine kinases of the src family.
Author(s) -
Köhr G,
Seeburg P H
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021320
Subject(s) - fyn , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , receptor tyrosine kinase , tyrosine protein kinase csk , nmda receptor , sh3 domain , tyrosine kinase , phosphorylation , kinase , biology , tyrosine phosphorylation , src family kinase , sh2 domain , chemistry , biochemistry , receptor , signal transduction
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.