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    题名: Protein Kinase CK2 Impairs Spatial Memory Formation through Differential Cross Talk with PI-3 Kinase Signaling: Activation of Akt and Inactivation of SGK1
    作者: 趙知章
    Chao,Chih Chang;Ma,Yun L.;Lee,Eminy H. Y.
    贡献者: 神科所
    关键词: protein kinase CK2;serum- and glucocorticoid-inducible kinase 1;Akt;protein phosphatase 2A;spatial memory formation;hippocampus
    日期: 2007.06
    上传时间: 2014-09-23 12:25:30 (UTC+8)
    摘要: Casein kinase II (CK2) is a multifunctional serine/threonine protein kinase that is associated with the development of neuritogenesis and synaptic plasticity. The phosphoinositide 3-kinase (PI-3K)/Akt pathway is implicated in long-term memory formation. In addition, serum- and glucocorticoid-inducible kinase 1 (SGK1) is another downstream target of PI-3K signaling that was shown to play an important role in spatial memory formation. Whether CK2 may also affect memory formation and whether CK2 interacts with Akt and SGK1 during this process is unknown. In the present study, we found that water maze training significantly decreased CK2 activity in the rat hippocampal CA1 area but not inthe dentate gyrus (DG) area. Transfection ofthe dominant negative mutant of CK2, CK2 A156,tothe CA1 area, but not to the DG area, decreased CK2 activity but enhanced spatial memory formation. Meanwhile, it increased SGK1 phosphorylation at Ser422, decreased Akt phosphorylation at Ser473, and increased cAMP response element-binding protein phosphorylation at Ser133. Transfection ofthe constitutively active SGK1, SGKS422D, enhanced whereastransfection ofthe wild-type Aktimpaired spatial memory formation. Also, administration of the protein phosphatase 2A inhibitor, fostriecin, reversed the memory-impairing effect of CK2 WT. It also reversed the effect of CK2 WT in decreasing SGK1 phosphorylation. Akt Ser473 phosphorylation was moderately increased by CK2 WT and fostriecin treatment, but AktS473A mutant transfection reversed the memory-impairing effect of CK2 WT. These results together suggest that CK2 impairs spatial memory formation through differential cross talk with PI-3 kinase signaling by activation of Akt and inactivation of SGK1 through protein phosphatase 2A.
    關聯: The Journal of Neuroscience,27(23),6243-6248
    数据类型: article
    DOI 連結: http://dx.doi.org/10.1523/JNEUROSCI.1531-07.2007
    DOI: 10.1523/JNEUROSCI.1531-07.2007
    显示于类别:[神經科學研究所] 期刊論文

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