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題名 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.
貢獻者 神科所
關鍵詞 protein kinase CK2; serum- and glucocorticoid-inducible kinase 1; Akt; protein phosphatase 2A; spatial memory formation;hippocampus
日期 2007.06
上傳時間 23-Sep-2014 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
資料類型 article
DOI http://dx.doi.org/10.1523/JNEUROSCI.1531-07.2007
dc.contributor 神科所en_US
dc.creator (作者) 趙知章zh_TW
dc.creator (作者) Chao,Chih Chang ; Ma,Yun L.; Lee,Eminy H. Y.en_US
dc.date (日期) 2007.06en_US
dc.date.accessioned 23-Sep-2014 12:25:30 (UTC+8)-
dc.date.available 23-Sep-2014 12:25:30 (UTC+8)-
dc.date.issued (上傳時間) 23-Sep-2014 12:25:30 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/70089-
dc.description.abstract (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.en_US
dc.format.extent 373661 bytes-
dc.format.mimetype application/pdf-
dc.language.iso en_US-
dc.relation (關聯) The Journal of Neuroscience,27(23),6243-6248en_US
dc.subject (關鍵詞) protein kinase CK2; serum- and glucocorticoid-inducible kinase 1; Akt; protein phosphatase 2A; spatial memory formation;hippocampusen_US
dc.title (題名) Protein Kinase CK2 Impairs Spatial Memory Formation through Differential Cross Talk with PI-3 Kinase Signaling: Activation of Akt and Inactivation of SGK1en_US
dc.type (資料類型) articleen
dc.identifier.doi (DOI) 10.1523/JNEUROSCI.1531-07.2007-
dc.doi.uri (DOI) http://dx.doi.org/10.1523/JNEUROSCI.1531-07.2007-