Fukunaga K, Soderling T R, Miyamoto E
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
J Biol Chem. 1992 Nov 5;267(31):22527-33.
In cultured rat hippocampal neurons, glutamate elevated the Ca(2+)-independent activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) through autophosphorylation when the neurons were incubated in Mg(2+)-free buffer, and this response was blocked by specific antagonists of the N-methyl-D-aspartate (NMDA) receptor. In addition, glutamate stimulated the transient translocation of protein kinase C (PKC) from the cytosol to the membrane fraction. This effect was not blocked by NMDA receptor antagonists but was partially blocked by DL-2-amino-3-phosphonopropionate. Quisqualate or trans-1-amoinocyclopentane-trans1,3-dicarboxylate produced a similar effect on the translocation of PKC. In the experiments with 32P-labeled cells, the phosphorylation of microtuble-associated protein 2 and synapsin I, as well as autophosphorylation of CaM kinase II, were found to be stimulated by exposure to glutamate. These results suggest that glutamate can activate CaM kinase II through the ionotropic NMDA receptor, which in turn increases the phosphorylation of microtuble-associated protein 2 and synapsin I. PKC was activated through the metabotropic glutamate receptor in the hippocampal neurons.
在培养的大鼠海马神经元中，当神经元在无镁缓冲液中孵育时，谷氨酸通过自身磷酸化提高了钙调蛋白依赖性蛋白激酶II（CaM激酶II）的非钙依赖性活性，并且这种反应被N-甲基-D-天冬氨酸（NMDA）受体的特异性拮抗剂所阻断。此外，谷氨酸刺激蛋白激酶C（PKC）从细胞质向膜部分的瞬时转位。这种效应不被NMDA受体拮抗剂阻断，但被DL-2-氨基-3-膦酰丙酸部分阻断。quisqualate或反式-1-氨基环戊烷-反式-1,3-二羧酸对PKC的转位产生类似的效应。在用32P标记细胞的实验中，发现暴露于谷氨酸会刺激微管相关蛋白2和突触素I的磷酸化以及CaM激酶II的自身磷酸化。这些结果表明，谷氨酸可以通过离子型NMDA受体激活CaM激酶II，进而增加微管相关蛋白2和突触素I的磷酸化。PKC在海马神经元中通过代谢型谷氨酸受体被激活。
