αCaMKII binding to the C-terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation
αCaMKII binding to the C-terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation
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DOI：
10.1016/s0014-5793(99)00985-0
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发表时间：
1999-08-13
期刊：
影响因子：
3.5
通讯作者：
Di Luca, M
中科院分区：
文献类型：
--
作者：
Gardoni, F;Schrama, LH;Di Luca, M
Ca 2 +/钙调素依赖性蛋白激酶II（CaMKII）是一种多功能的、广泛分布的酶，在突触后致密物（PSD）中富集。在这里，我们证明CaMKII结合NMDA受体NR 2A亚基的离散C-末端区域并促进该NMDA受体亚基的Ser残基的磷酸化，在“拉出”和重叠实验中，谷胱甘肽S-转移酶（GST）-NR 2A（1349-1464）与来自溶解海马PSD的天然CaMKII结合，并且这种结合受到重组α CaMKII（1-315）的竞争。较长的GST-NR 2A（1244-1464）虽然含有CaMKII磷酸位点Ser-1289，但以较低的效力结合激酶。CaMKII与NR 2A（1349-1464）的结合在Ca 2 +/钙调蛋白存在下通过激酶自磷酸化正调节。这些数据为调节突触强度的机制提供了直接证据。(C)1999年欧洲生物化学学会联合会。
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 alpha CaMKII(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. (C) 1999 Federation of European Biochemical Societies.