Li B S, Sun M K, Zhang L, Takahashi S, Ma W, Vinade L, Kulkarni A B, Brady R O, Pant H C
Laboratory of Neurochemistry, Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12742-7. doi: 10.1073/pnas.211428098. Epub 2001 Oct 2.
Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.
N-甲基-D-天冬氨酸（NMDA）类谷氨酸受体（NMDARs）成员对发育、突触传递、学习和记忆至关重要；它们是中枢神经系统病理紊乱的靶点。NMDARs可被丝氨酸/苏氨酸激酶和酪氨酸激酶磷酸化。在此，我们证明细胞周期蛋白依赖性激酶5（Cdk5）在体外和完整细胞中与NR2A亚基结合并使其在Ser-1232位点磷酸化。此外，我们表明，选择性Cdk5抑制剂roscovitine可阻断大鼠CA1海马神经元中的长时程增强诱导和NMDA诱发电流。这些结果表明，Cdk5通过上调NMDARs在突触传递和可塑性中起关键作用。
