2002 年度実績報告書

時計遺伝子産物のリン酸化に関わる分子素過程の解明

研究課題

研究課題/領域番号	11233205
研究機関	東北大学
研究代表者	福永浩司東北大学, 大学院・薬学研究科, 教授 (90136721)
研究分担者	森山芳則岡山大学, 薬学部, 教授 (10150658) 滝口正樹千葉大学, 大学院・医学研究院, 教授 (40179578)
キーワード	CaMキナーゼII / 時計遺伝子 / 視交叉上核 / 概日リズム / マイクロアレイ / フィブリノーゲン / 松果体 / グルタミン酸
研究概要	Ca^<2+>/カルモデュリン依存性プロテインキナーゼII(CaMキナーゼII)は視交叉上核において時計遺伝子のPer1とPer2の発現に関与している。福永らはmPer1遺伝子の上流7.2k(mPer1-7.2k)のプロモーターを用いて、CaMキナーゼIIによるmPer1誘導機構について解析した。mPer1-7.2kにルシフェラーゼをつないだレポーター遺伝子とCaMキナーゼII、MEKK, cAMPキナーゼの恒常的活性型酵素をNG108-15細胞に導入し、ルシフェラーゼ活性を指標にしてプロモーター活性を測定した。MEKKとcAMPキナーゼが1.5倍にCaMキナーゼIIが3倍にプロモーター活性を上昇させた。しかし、mPer1のプロモーター活性の上昇は発現させる細胞で異なっており、発現のシグナル伝達系は細胞で異なることが示唆された。デリーションしたプロモーターを用いた実験からCaMキナーゼIIの反応エレメントはexon 1Bの上流に存在するSP-1結合部位であるGC-boxであることが明らかとなった。以上の結果は、mPer1遺伝子がCaMキナーゼIIによって転写レベルで調節されることを示唆している。滝口らはマウス肝臓より抽出したpoly(A)+RNAを用いて、約2,300種類のマウス肝臓cDNAをスポットした自家製チップによるマイクロアレイ解析を行った。フィブリノーゲン遺伝子の二峰性発現が時計遺伝子の制御下にあることを明らかにした。森山らは概日リズムの出力系である松果体において、グルタミン酸を伝達物質とする新しいserotonin-N-acetyltransferase (NAT)制御系の存在を明らかにした。NAT自身が内在するレドックス制御系も見出した。

研究成果

(29件)

すべてその他

すべて文献書誌 (29件)

[文献書誌] Kanasaki, H.: "Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells"Biol.Reproduction.. 67. 107-113 (2002)
[文献書誌] 福永浩司: "長期増強とCaMキナーゼ"Clinical Neuroscience. 20. 618-619 (2002)
[文献書誌] Takeuchi, Y.: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor gene expression by stimulation of dopamine D2 receptor in transfected NG108-15 cells"J.Neurochem.. 82. 316-328 (2002)
[文献書誌] Kawano, T.: "Decreased Akt activity is associated with activation of forkhead transcription factor after transient forebrain ischemia in gerbil hippocampus"J.Cereb. Blood Flow Metab.. 22. 926-934 (2002)
[文献書誌] Uezu, A.: "Activation of Ca^<2+>/calmodulin-dependent protein kinase I in cultured rat hippocampal neurons"J.Neurochem.. 82. 585-593 (2002)
[文献書誌] Osuka, K.: "Phosphorylation of neuronal nitric oxide synthase at Ser^<847> CaM-KII in the hippocampus of rat brain after transient forebrain ischemia"J.Cereb. Blood Flow Metab.. 22. 1098-1106 (2002)
[文献書誌] Sakurada, K: "Synapsin I is phosphorylated at Ser^<603> by p21-activated kinases (PAKs) in vitro and in PC12 cells stimulated with bradykinin"J.Biol.Chem.. 277. 45473-47479 (2002)
[文献書誌] Takeuchi, Y.: "Activation of the rat dopamine D2 receptor promoter by mitogen-activated protein kinase and Ca^<2+>/calmodulin-dependent protein kinase II pathways"J.Neurochem.. 83. 784-796 (2002)
[文献書誌] Fukunaga, K.: "Ca^<2+>/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin"J.Neurosci.Res.. 70. 799-807 (2002)
[文献書誌] Kanasaki, H.: "Regulation of gonadotropin a subunit gene expression by dopamine D_2, receptor agonist in clonal mouse gonadotroph αT3-1 cells"Biol. Reproduction. 67. 1218-1224 (2002)
[文献書誌] Li, X.-L.: "Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents"Neuroscience. 113. 607-615 (2002)
[文献書誌] Fueta, Y.: "Hyperexcitability and changes in activities of Ca^<2+>/calmodulin-dependent kinase II and mitogen-activated protein kinase in the hippocampus of rats exposed to 1-bromopropane"Life Science. 72. 521-529 (2002)
[文献書誌] Nomura, K.: "Involvement of calcium/calmodulin-dependent protein kinase II in the induction of mPer1"J.Neurosci.Res.. (in press). (2003)
[文献書誌] Takeuchi, Y.: "Differential regulation of NF-κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108-15 cells"J.Neurochem.. (in press). (2003)
[文献書誌] Takeuchi, Y.: "Differential subcellular localiztion of two dopamine D2 receptor isoforms in transfected NG108-15 cells"J.Neurochem.. (in press). (2003)
[文献書誌] Nishimura, H.: "Cloning, characterization, and expression of two alternatively splicing isoforms of Ca^<2+>/calmodulin-dependent protein kinase Iγ in the brain"J.Neurochem.. (in press). (2003)
[文献書誌] Akiba, T.: "Expression and regulation of the gene for arginase I in mouse salivary glands : requirement of CCAAT/enhancer-binding protein a for the expression in the parotid gland"J.Biochem.. 132. 621-627 (2002)
[文献書誌] Hiwasa, T.: "Decrease in growth factor receptors after treatment with serine protease inhibitor ONO-3403"Int.J.Oncol.. 20. 787-802 (2002)
[文献書誌] Shimada, H.: "Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells"Oncogene. 21. 1208-1216 (2002)
[文献書誌] Hiwasa, T.: "Regulation of transformed state by calpastatin via PKCε in NIH3T3 mouse fibroblasts"Biochem.Biophys.Res.Commun. 290. 510-517 (2002)
[文献書誌] Yamada, H.: "Norepinephrine triggers Ca^<2+>-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture"J.Neurochem.. 81. 533-540 (2002)
[文献書誌] Hatashi, M.: "The internal pH of synaptic-like microvesicles in rat pinealocytes in culture"J.Neurochem.. 82. 698-704 (2002)
[文献書誌] Tsuboi, S.: "An intramolecular disulfide bridge as a catalytic switch for serotonin N-acetyltransferase"J.Biol.Chem.. 277. 44229-44235 (2002)
[文献書誌] Morimoto, R.: "Co-expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and their association with synaptic-like microvesicles in rat pinealocytes"J.Neurochem.. 84. 382-391 (2003)
[文献書誌] Hayashi, M.: "Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers a glutamatergic signal transmisson in islets of Langerhans"J.Biol.Chem.. 278. 1966-1974 (2003)
[文献書誌] Moriyama, Y.: "Vacuolar proton pumps in malaria parasite cells"J.Bioenerg.Biomembr.. (in press). (2003)
[文献書誌] Hayashi, M.: "Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alpha cells of islet of Langerhans"Diabetes. (in press). (2003)
[文献書誌] 高森茂雄: "グルタミン酸化学伝達の鍵分子:小胞型グルタミン酸トランスポーター"細胞工学. (in press). (2003)
[文献書誌] Fukunaga, K.: "Recent Research Developments in Neurochemistry (ed.: S.G.Pandalai), Differential role of CaM kinases II and IV activities in neuronal plasticity and memory"Research Signpost, Kerala, India. 16 (2002)

2002 年度 実績報告書

時計遺伝子産物のリン酸化に関わる分子素過程の解明

研究代表者

福永 浩司 東北大学, 大学院・薬学研究科, 教授 (90136721)

研究成果

[文献書誌] Kanasaki, H.: "Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells"Biol.Reproduction.. 67. 107-113 (2002)

[文献書誌] 福永浩司: "長期増強とCaMキナーゼ"Clinical Neuroscience. 20. 618-619 (2002)

[文献書誌] Takeuchi, Y.: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor gene expression by stimulation of dopamine D2 receptor in transfected NG108-15 cells"J.Neurochem.. 82. 316-328 (2002)

[文献書誌] Kawano, T.: "Decreased Akt activity is associated with activation of forkhead transcription factor after transient forebrain ischemia in gerbil hippocampus"J.Cereb. Blood Flow Metab.. 22. 926-934 (2002)

[文献書誌] Uezu, A.: "Activation of Ca^<2+>/calmodulin-dependent protein kinase I in cultured rat hippocampal neurons"J.Neurochem.. 82. 585-593 (2002)

[文献書誌] Osuka, K.: "Phosphorylation of neuronal nitric oxide synthase at Ser^<847> CaM-KII in the hippocampus of rat brain after transient forebrain ischemia"J.Cereb. Blood Flow Metab.. 22. 1098-1106 (2002)

[文献書誌] Sakurada, K: "Synapsin I is phosphorylated at Ser^<603> by p21-activated kinases (PAKs) in vitro and in PC12 cells stimulated with bradykinin"J.Biol.Chem.. 277. 45473-47479 (2002)

[文献書誌] Takeuchi, Y.: "Activation of the rat dopamine D2 receptor promoter by mitogen-activated protein kinase and Ca^<2+>/calmodulin-dependent protein kinase II pathways"J.Neurochem.. 83. 784-796 (2002)

[文献書誌] Fukunaga, K.: "Ca^<2+>/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin"J.Neurosci.Res.. 70. 799-807 (2002)

[文献書誌] Kanasaki, H.: "Regulation of gonadotropin a subunit gene expression by dopamine D_2, receptor agonist in clonal mouse gonadotroph αT3-1 cells"Biol. Reproduction. 67. 1218-1224 (2002)

[文献書誌] Li, X.-L.: "Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents"Neuroscience. 113. 607-615 (2002)

[文献書誌] Fueta, Y.: "Hyperexcitability and changes in activities of Ca^<2+>/calmodulin-dependent kinase II and mitogen-activated protein kinase in the hippocampus of rats exposed to 1-bromopropane"Life Science. 72. 521-529 (2002)

[文献書誌] Nomura, K.: "Involvement of calcium/calmodulin-dependent protein kinase II in the induction of mPer1"J.Neurosci.Res.. (in press). (2003)

[文献書誌] Takeuchi, Y.: "Differential regulation of NF-κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108-15 cells"J.Neurochem.. (in press). (2003)

[文献書誌] Takeuchi, Y.: "Differential subcellular localiztion of two dopamine D2 receptor isoforms in transfected NG108-15 cells"J.Neurochem.. (in press). (2003)

[文献書誌] Nishimura, H.: "Cloning, characterization, and expression of two alternatively splicing isoforms of Ca^<2+>/calmodulin-dependent protein kinase Iγ in the brain"J.Neurochem.. (in press). (2003)

[文献書誌] Akiba, T.: "Expression and regulation of the gene for arginase I in mouse salivary glands : requirement of CCAAT/enhancer-binding protein a for the expression in the parotid gland"J.Biochem.. 132. 621-627 (2002)

[文献書誌] Hiwasa, T.: "Decrease in growth factor receptors after treatment with serine protease inhibitor ONO-3403"Int.J.Oncol.. 20. 787-802 (2002)

[文献書誌] Shimada, H.: "Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells"Oncogene. 21. 1208-1216 (2002)

[文献書誌] Hiwasa, T.: "Regulation of transformed state by calpastatin via PKCε in NIH3T3 mouse fibroblasts"Biochem.Biophys.Res.Commun. 290. 510-517 (2002)

[文献書誌] Yamada, H.: "Norepinephrine triggers Ca^<2+>-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture"J.Neurochem.. 81. 533-540 (2002)

[文献書誌] Hatashi, M.: "The internal pH of synaptic-like microvesicles in rat pinealocytes in culture"J.Neurochem.. 82. 698-704 (2002)

[文献書誌] Tsuboi, S.: "An intramolecular disulfide bridge as a catalytic switch for serotonin N-acetyltransferase"J.Biol.Chem.. 277. 44229-44235 (2002)

[文献書誌] Morimoto, R.: "Co-expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and their association with synaptic-like microvesicles in rat pinealocytes"J.Neurochem.. 84. 382-391 (2003)

[文献書誌] Hayashi, M.: "Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers a glutamatergic signal transmisson in islets of Langerhans"J.Biol.Chem.. 278. 1966-1974 (2003)

[文献書誌] Moriyama, Y.: "Vacuolar proton pumps in malaria parasite cells"J.Bioenerg.Biomembr.. (in press). (2003)

[文献書誌] Hayashi, M.: "Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alpha cells of islet of Langerhans"Diabetes. (in press). (2003)

[文献書誌] 高森茂雄: "グルタミン酸化学伝達の鍵分子:小胞型グルタミン酸トランスポーター"細胞工学. (in press). (2003)

[文献書誌] Fukunaga, K.: "Recent Research Developments in Neurochemistry (ed.: S.G.Pandalai), Differential role of CaM kinases II and IV activities in neuronal plasticity and memory"Research Signpost, Kerala, India. 16 (2002)

2002 年度実績報告書

福永浩司東北大学, 大学院・薬学研究科, 教授 (90136721)