Nakazawa Takanobu, Tezuka Tohru, Yamamoto Tadashi
Division of Oncology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Oct;22(5):165-7.
The ionnotropic glutamate receptor, N-methyl-D-aspartate (NMDA) receptor, is a prominent ligand-gated and voltage-gated ion channel in excitatory synaptic transmission in the mammalian central nervous system. The NMDA channel is also regulated by its phosphorylation. We have shown that an Src family kinase Fyn phosphorylates NR2A and NR2B subunits of the NMDA receptor. The phosphorylation events are facilitated by the presence of PSD-95, which is quite likely due to the complex formation of Fyn, PSD-95, and the NMDA receptor: Fyn interacts with PSD-95 and PSD-95 interacts with the NMDA receptor. We have identified tyrosine phosphorylation sites on NR2A and NR2B. A phosphorylation of one of the sites on NR2B (Tyr1472) is largely dependent on Fyn and is elevated upon the LTP induction of hippocampal CA1 neurons. The data suggest that Tyr-1472 phosphorylation of NR2B is important for synaptic plasticity. A phosphorylation of the other tyrosine residues of NR2A and NR2B would also be involved in brain development and function.
离子型谷氨酸受体，即N-甲基-D-天冬氨酸（NMDA）受体，是哺乳动物中枢神经系统兴奋性突触传递中一种重要的配体门控和电压门控离子通道。NMDA通道也受其磷酸化调节。我们已经表明，Src家族激酶Fyn可使NMDA受体的NR2A和NR2B亚基磷酸化。PSD-95的存在促进了磷酸化事件，这很可能是由于Fyn、PSD-95和NMDA受体形成了复合物：Fyn与PSD-95相互作用，而PSD-95与NMDA受体相互作用。我们已经确定了NR2A和NR2B上的酪氨酸磷酸化位点。NR2B上其中一个位点（Tyr1472）的磷酸化很大程度上依赖于Fyn，并且在海马CA1神经元的长时程增强诱导后升高。数据表明，NR2B的Tyr-1472磷酸化对突触可塑性很重要。NR2A和NR2B其他酪氨酸残基的磷酸化也会参与大脑发育和功能。
