α-钙调蛋白激酶II与N-甲基-D-天冬氨酸受体亚基NR2A的C末端尾巴结合及其自磷酸化调节作用。

AlphaCaMKII binding to the C-terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation.

作者信息

Gardoni F, Schrama L H, van Dalen J J, Gispen W H, Cattabeni F, Di Luca M

机构信息

Institute of Pharmacological Sciences, University of Milano, Italy.

出版信息

FEBS Lett. 1999 Aug 13;456(3):394-8. doi: 10.1016/s0014-5793(99)00985-0.

DOI:10.1016/s0014-5793(99)00985-0

PMID:10462051

Abstract

Ca2+/calmodulin-dependent protein kinase II (CaMKII), a multifunctional, widely distributed enzyme, is enriched in post-synaptic densities (PSDs). Here, we demonstrate that CaMKII binds to a discrete C-terminal region of the NR2A subunit of NMDA receptors and promotes the phosphorylation of a Ser residue of this NMDA receptor subunit. Glutathione S-transferase (GST)-NR2A(1349-1464) binds native CaMKII from solubilised hippocampal PSDs in 'pull-out' and overlay experiments and this binding is competed by recombinant alphaCaMKII(1-315). The longer GST-NR2A(1244-1464), although containing the CaMKII phosphosite Ser-1289, binds the kinase with a lower efficacy. CaMKII association to NR2A(1349-1464) is positively modulated by kinase autophosphorylation in the presence of Ca2+/calmodulin. These data provide direct evidence for a mechanism modulating the synaptic strength.

摘要

钙离子/钙调蛋白依赖性蛋白激酶II（CaMKII）是一种多功能、分布广泛的酶，在突触后致密物（PSD）中含量丰富。在此，我们证明CaMKII与N-甲基-D-天冬氨酸受体（NMDA）的NR2A亚基的一个离散C末端区域结合，并促进该NMDA受体亚基一个丝氨酸残基的磷酸化。在“下拉”和覆盖实验中，谷胱甘肽S-转移酶（GST）-NR2A(1349 - 1464)与溶解的海马PSD中的天然CaMKII结合，并且这种结合被重组αCaMKII(1 - 315)竞争。较长的GST-NR2A(1244 - 1464)，尽管含有CaMKII磷酸化位点丝氨酸-1289，但与该激酶的结合效率较低。在Ca2+/钙调蛋白存在的情况下，激酶自身磷酸化对CaMKII与NR2A(1349 - 1464)的结合有正向调节作用。这些数据为调节突触强度的机制提供了直接证据。