PMID- 10195142
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20131121
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 1
IP  - 3
DP  - 1998 Jul
TI  - Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc
      inhibition.
PG  - 185-91
AB  - Activation of the tyrosine kinase Src potentiates NMDA-receptor currents, which
      is thought to be necessary for induction of hippocampal long-term potentiation.
      Although the carboxy(C)-terminal domain of the NR2A subunit contains potential
      tyrosine phosphorylation sites, the mechanisms by which Src modulates synaptic
      plasticity and NMDA receptor currents is not fully understood. Here we present
      evidence from NR1 mutants and splice variants that Src potentiates NMDA-receptor 
      currents by reducing the tonic inhibition of receptors composed of NR1 and NR2A
      subunits by extracellular zinc. Using site-directed mutagenesis, we have
      identified three C-terminal tyrosine residues of NR2A that are required for Src's
      modulation of the zinc sensitivity of NMDA receptors. Our data link two
      modulatory sites of NMDA receptors that were previously thought to be
      independent.
FAU - Zheng, F
AU  - Zheng F
AD  - Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia
      30322, USA. fzheng@emory.edu
FAU - Gingrich, M B
AU  - Gingrich MB
FAU - Traynelis, S F
AU  - Traynelis SF
FAU - Conn, P J
AU  - Conn PJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Chelating Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 42HK56048U (Tyrosine)
RN  - 9G34HU7RV0 (Edetic Acid)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
CIN - Nat Neurosci. 1998 Jul;1(3):173-5. PMID: 10195137
MH  - Cell Line
MH  - Chelating Agents/pharmacology
MH  - Drug Resistance
MH  - Edetic Acid/pharmacology
MH  - Electric Conductivity
MH  - Humans
MH  - Peptide Fragments/physiology
MH  - Protein-Tyrosine Kinases/*physiology
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*physiology
MH  - Tyrosine/chemistry/physiology
MH  - Zinc/*antagonists & inhibitors/metabolism/pharmacology
MH  - src-Family Kinases/pharmacology
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1998/03/11 00:00 [received]
PHST- 1998/05/22 00:00 [accepted]
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1038/634 [doi]
AID - 634 [pii]
PST - ppublish
SO  - Nat Neurosci. 1998 Jul;1(3):185-91. doi: 10.1038/634.