TY - JOUR T1 - Modulation of Protein Tyrosine Phosphatase Activity Alters the Subunit Assembly in Native <em>N</em>-Methyl-<span class="sc">d</span>-aspartate Receptor Complex JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 86 LP - 93 DO - 10.1124/jpet.105.083535 VL - 314 IS - 1 AU - Karima Ferrani-Kile AU - Steven W. Leslie Y1 - 2005/07/01 UR - http://jpet.aspetjournals.org/content/314/1/86.abstract N2 - The N-methyl-d-aspartate (NMDA) receptor is crucial for development and neuroplasticity as well as excitotoxicity. The biochemical basis of the disassembly and reassembly of NMDA receptor has never been reported. Using coimmunoprecipitation, Western blotting, and mass spectrometry, we show that inhibition of tyrosine phosphatases triggers disassembly of NR1, NR2A, and NR2B in cortical NMDA receptor complexes. Furthermore, the disassembly of the NMDA receptor subunits is immediate, dose-dependent, and reversible and seems to occur through mechanisms linked to Src kinases. Together, these results define a novel role for tyrosine phosphatases in the complex mechanism of NMDA receptor regulation. The American Society for Pharmacology and Experimental Therapeutics ER -