PMID- 11158244
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 76
IP  - 3
DP  - 2001 Feb
TI  - Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B 
      subunits of the NMDA receptor.
PG  - 737-44
AB  - The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, 
      which plays crucial roles in synaptic plasticity and development. We have 
      recently shown that potentiation of NMDA receptor function by protein kinase C 
      (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. The 
      aim of this study was to test whether this effect could be mediated by direct 
      tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. Following 
      treatment of rat hippocampal CA1 mini-slices with 500 nM phorbol 12-myristate 
      13-acetate (PMA) for 15 min, samples were homogenized, immunoprecipitated with 
      anti-NR2A or NR2B antibodies and the resulting pellets subjected to Western 
      blotting with antiphosphotyrosine antibody. An increase in tyrosine 
      phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was 
      observed. This increase was blocked by pretreatment with the selective PKC 
      inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with 
      the Src family tyrosine kinase inhibitor PP2. PMA treatment also produced an 
      increase in the phosphorylation of serine 890 on the NR1 subunit, a known PKC 
      site, at 5 min with phosphorylation returning to near basal levels by 10 min 
      while tyrosine phosphorylation of NR2A and NR2B was sustained for up to 15 min. 
      These results suggest that the modulation of NMDA receptor function seen with PKC 
      activation may be the result of tyrosine phosphorylation of NR2A and/or NR2B.
FAU - Grosshans, D R
AU  - Grosshans DR
AD  - Department of Pharmacology, Program in Neuroscience, University of Colorado 
      Health Sciences Center, Denver, Colorado, USA.
FAU - Browning, M D
AU  - Browning MD
LA  - eng
GR  - AA09675/AA/NIAAA NIH HHS/United States
GR  - AG04418/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Drug Synergism
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/*metabolism
MH  - In Vitro Techniques
MH  - Okadaic Acid/pharmacology
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Time Factors
MH  - Tyrosine/*metabolism
EDAT- 2001/02/07 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1046/j.1471-4159.2001.00034.x [doi]
PST - ppublish
SO  - J Neurochem. 2001 Feb;76(3):737-44. doi: 10.1046/j.1471-4159.2001.00034.x.