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2008 Fiscal Year Final Research Report

Mechanism and treatment for the disease caused by the impairment of PKC signaling

Research Project

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Project/Area Number 19390064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKobe University

Principal Investigator

SAITO Naoaki  Kobe University, 自然科学系先端融合研究環バイオシグナル研究センター, 教授 (60178499)

Co-Investigator(Kenkyū-buntansha) SHIRAI Yasuhito  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 准教授 (60263399)
UEYAMA Takehiko  神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 講師 (80346254)
Project Period (FY) 2007 – 2008
KeywordsプロテインキナーゼC / 精髄小脳変性症 / カルシウム / 神経変性 / 遺伝子変異
Research Abstract

脊髄小脳変性症14型の発症メカニズムとして、変異型PKCγには細胞膜に十分な時間存在する能力が欠如しTRPCチャネルをリン酸化することができないため細胞外からのCa^<2+> 流入を抑制する機構が働かないことを示した。この過剰なCa^<2+> 流入が神経細胞死が招くと推測された。また他の要因として初代培養プルキンエ細胞において変異型PKCγは凝集体の形成・樹状突起の伸展・シナプス形成異常を引き起こす事を示した。

  • Research Products

    (40 results)

All 2009 2008 2007 2006 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (23 results)

  • [Journal Article] Kinase activity of the dgk gene product is involved 1 in the virulence of Streptococcus mutans Microbiology2009

    • Author(s)
      Shibata, Y., van der Ploeg, JR., Kozuki, T., Shirai, Y., Saito, N., Kawada, M., Takeshita, T., and Yamashita, Y.
    • Journal Title

      155

      Pages: 557-565

    • Peer Reviewed
  • [Journal Article] Mutant γPKC found in spinocerebellar ataxia type 14 induces aggregate-independent maldevelopment of dendrites in primary cultured Purkinje cells2009

    • Author(s)
      Seki, T. ; Shimahara ; T., Yamamoto ; K., Abe ; N., Amano, T. ; Adachi ; N., Takahashi, H. ; Kashiwagi, K. ; Saito, N., Sakai, N.
    • Journal Title

      Neurobiology of Disease 33

      Pages: 260-273

    • Peer Reviewed
  • [Journal Article] Diacylglycerol kinase β accumulates on the perisynaptic site of medium spiny neurons in the striatum2008

    • Author(s)
      Hozumi,Y., Fukaya, M., Adachi, N., Saito, N., Otani, K., Kondo, K., Watanabe, M., and Goto, K.
    • Journal Title

      Eur. J. Neurosci 28

      Pages: 2409-2422

    • Peer Reviewed
  • [Journal Article] Ca^<2+> oscillation induced by P2Y2 receptor activation and its regulation by a neuron-specific subtype of PKC (βPKC)2008

    • Author(s)
      Ashida, N., Ueyama, T., Rikitake, K., Shirai, Y. Eto, M., Kondoh, T., Kohmura, E., and Saito, N.
    • Journal Title

      Neurosci. Lett 446

      Pages: 123-128

    • Peer Reviewed
  • [Journal Article] Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma2008

    • Author(s)
      Ohtani, Y., Harada, T., Funasaka, Y., Nakao, K., Takahara, C., Abdel-Daim, M., Sakai, N., Saito, N., Nishigori, C. and Aiba, A.
    • Journal Title

      Oncogene 27

      Pages: 7162-7170

    • Peer Reviewed
  • [Journal Article] Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain2008

    • Author(s)
      Ibi, M., Matsuno, K., Shiba, D., Katsuyama, M., Iwata, K., Kakehi, T., Nakagawa, T., Sango, K., Shirai, Y., Yokoyama, T., Kaneko, S., Saito N.,and Yabe-Nishimura, C.
    • Journal Title

      J. Neurosci 28

      Pages: 9486-9494

    • Peer Reviewed
  • [Journal Article] Minireview : Protein kinase Cε-function in neurons2008

    • Author(s)
      Shirai, Y., Adachi, N. and Saito, N.
    • Journal Title

      FEBS J 275

      Pages: 3988-3994

    • Peer Reviewed
  • [Journal Article] Enzymological analysis of mutant protein kinase Cγ causing spinocerebellar ataxia type 14 and its dysfunction in Ca^<2+> homeostasis2008

    • Author(s)
      Adachi, N., Kobayashi, T., Takahashi, H., Kawasaki, T., Shirai, Y., Ueyama, T., Matsuda, T., Seki, T., Sakai, N. and Saito N.
    • Journal Title

      J. Biol. Chem 283

      Pages: 19854-19863

    • Peer Reviewed
  • [Journal Article] Identification of SF-1/Ad4BP gene expression modulators by large scale gain and loss of function studies2008

    • Author(s)
      Sakai, N., Terami, H., Suzuki, S., Haga, M.,Nomoto, K., Tsuchida, N., Morohashi, KI.,Saito, N., Asada, M., Hashimoto, M.,Harada, D., Asahara, H., Ishikawa, T.,Shimada, F., Sakurada, K.
    • Journal Title

      J. Endocrinol 198

      Pages: 489-497

    • Peer Reviewed
  • [Journal Article] Sequential Binding of Cytosolic Phox Complex to Phagosomes through Regulated Adaptor Proteins : Evaluation Using the Novel Monomeric Kusabira-Green System and Live Imaging of Phagocytosis2008

    • Author(s)
      Ueyama, T., Kusakabe, T., Karasawa, S., Kawasaki, T., Shimizu, A., Son J-H, Shirai, Y., Leto, TL., Miyawaki, A., and Saito N.
    • Journal Title

      J. Immunol 181

      Pages: 629-40

    • Peer Reviewed
  • [Journal Article] Lck-dependent tyrosine phosphorylation of DGK alpha regulates its membrane association in T cells2008

    • Author(s)
      Merino, E. Avila-Flores, A., Shirai, Y., Moraga, I., Saito, N. and Merida, I.
    • Journal Title

      J. Immunol 180

      Pages: 5805-5815

    • Peer Reviewed
  • [Journal Article] Immunogold electron microscopic demonstration of distinct submembranous localization of the activated γPKC depending on the stimulation2008

    • Author(s)
      Oyasu, M., Fujimiya, M., Kashiwagi, K., Ohmori, S., Imaeda, H. and Saito, N.
    • Journal Title

      J. Histochem. Cytochem 56

      Pages: 253-265

    • Peer Reviewed
  • [Journal Article] Synthesis Conformational Analysis, and Biological Evaluation of 1-Hexyl-indolactam-V10 as a Selective Activator for Novel Protein Kinase C Isozymes2008

    • Author(s)
      Yanagita, RC, Nakagawa, Y., Yamanaka, N., Kashiwagi, K., Saito, N. and Irie, K.
    • Journal Title

      J. Med. Chem 51

      Pages: 46-56

    • Peer Reviewed
  • [Journal Article] Regulation of Clathrin Dependent Endocytosis by Diacylglycerol kinaseδ2008

    • Author(s)
      Kawasaki, T., Kobayashi, T., Ueyama, T., Shirai, Y. and Saito, N.
    • Journal Title

      -Importance of Kinase Activity and Binding to AP2α-Biochem. J 409

      Pages: 471-479

    • Peer Reviewed
  • [Journal Article] Aggregate Formation of Mutant Protein Kinase C Gamma Found in Spinocerebellar Ataxia Type 14 Impairs Ubiquitin Proteasome System and Induces Endoplasmic Reticulum Stress Eur2007

    • Author(s)
      Seki, T., Takahashi, T., Adachi, N., Shimahara, T., Abe, N., Saito, N. and Sakai N.
    • Journal Title

      J. Neurosci 26

      Pages: 3126-3140

    • Peer Reviewed
  • [Journal Article] A novel PIP2 binding of εPKC and its contribution to the neurite induction ability2007

    • Author(s)
      Shirai, Y., Murakami, T., Kuramasu, M., Iijima L., and Saito, N.
    • Journal Title

      J. Neurochem 102

      Pages: 1635-1644

    • Peer Reviewed
  • [Journal Article] A Simple Analog of Tumor-promoting Aplysiatoxin Is an Antineoplastic Agent rather than a Tumor Promoter : Development of a Synthetically Accessible PKC Activator with Bryostatin-like Activity

    • Author(s)
      Yu Nakagawa, Y. Yanagita, RC, Hamada, N. Murakami, A. Takahashi, H. Saito, N. Nagai, H. and Irie, K.
    • Journal Title

      J Am. Chem. Soc (in press)

    • Peer Reviewed
  • [Presentation] 神経特異的ジアシルグリセロールキナーゼDGKβの機能解析2009

    • Author(s)
      上月健、白井康仁、掛札賢一、大八木篤、堀江恭二、嶋澤雅光、福永浩司、竹田潤二、齋藤尚亮、原英彰
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20090316-18
  • [Presentation] 気分障害と神経特異的ジアシルグリセロール2009

    • Author(s)
      白井康仁、齋藤尚亮
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20090316-18
  • [Presentation] マウス初代培養表皮細胞におけるRac3のRac1代償機能2009

    • Author(s)
      清水彩、上山健彦、坂原瑞穂、饗場篤、齋藤尚亮
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
  • [Presentation] 神経特異的ジアシルグリセロールキナーゼDGKβの機能解析2008

    • Author(s)
      白井康仁、上月健、掛札賢一、大八木篤、堀江恭二、嶋澤雅光、竹田潤二、齋藤尚亮、原英彰
    • Organizer
      BMB2008(第31回日本分子生物学会年会・第81回日本生化学大会合同大会)
    • Place of Presentation
      神戸
    • Year and Date
      20081209-11
  • [Presentation] NADPH oxidaseファミリーの活性化機構とその生理機能2008

    • Author(s)
      上山健彦
    • Organizer
      第3回グローバルCOE研究討論会
    • Place of Presentation
      淡路島(兵庫)
    • Year and Date
      20080701-02
  • [Presentation] Sequential binding of cytosolic phox complex to phagosomes through regulated adaptor proteins : evaluation using the novel monomeric Kusabira-Green(mKG)system and liveimaging of phagocytosis2008

    • Author(s)
      Ueyama,T., Kusakabe,T., Karasawa,S., Kawasaki,T., Shimizu,A., Son, Jeong-hyun., Leto,L.Thomas., Miyawaki,A., Saito,N.
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      ボストン
    • Year and Date
      20080601-07
  • [Presentation] Recessive embryonic lethality in mutant mice carrying a gene trap in intron 3 of RKIP-1 gene(92)2008

    • Author(s)
      Uo,M., Ohmori,S., Nakao,K., Saito,N.
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20080317-19
  • [Presentation] Differential regulation of dual oxidase 1 by dual activator 1 splicing variants2008

    • Author(s)
      Tsujibe,S., Ueyama,T., Shirai,Y., Leto L. Thomas., Saito,N.
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20080317-19
  • [Presentation] Sequential targeting of cytosolic phox proteins to phagosomes through regulated adaptor proteins during Fc□R-mediated phagocytosis2008

    • Author(s)
      Ueyama,T., Kusakabe,T., Karasawa,S., Kawasaki,T., Shimizu,A., Son,eong-hyun., Leto L.Thomas
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
  • [Presentation] Enzymological properties of PKCγ mutants found in spinocerebellar ataxia 14(SCA14) and its involvement in neuronal death2007

    • Author(s)
      Saito,N., Adachi,N., Takahashi,H., Kobayashi,T., Seki,T. Sakai,N.
    • Organizer
      International symposium on cell signaling and gene regulation
    • Place of Presentation
      Taiwan
    • Year and Date
      20071118-19
  • [Presentation] Live imaging of PKC signaling and its implication in neuronal disease2007

    • Author(s)
      Naoaki Saito
    • Organizer
      14^<th> Congress of Ca2+ binding proteins & Ca2+ function in health & disease
    • Place of Presentation
      La Palma Spain
    • Year and Date
      20071016-21
  • [Presentation] Dysfunction of intracellular Ca2+ regulation in SCA142007

    • Author(s)
      Adachi,N., Kobayashi,T., Seki,T., Sakai,N., Saito, N.
    • Organizer
      14^<th> Congress of Ca2+ binding proteins & Ca2+ function in health & disease
    • Place of Presentation
      La Palma Spain
    • Year and Date
      20071016-21
  • [Presentation] Clarification of regulatory mechanism of Orail(SOCs)by PKC2007

    • Author(s)
      Kawasaki,T., Ueyama,T., Shirai,Y., Saito, N.
    • Organizer
      14^<th> Congress of Ca2+ binding proteins & Ca2+ function in health & disease
    • Place of Presentation
      La Palma Spain
    • Year and Date
      20071016-21
  • [Presentation] 緑色蛍光蛋白(GFP)発現バイオ試料の半導体レーザ超短パルス光源による2光子イメージング2007

    • Author(s)
      佐藤綾耶、高島啓次郎、郭亨長、牟禮勝仁、横山弘之、坪川宏、齋藤尚亮
    • Organizer
      第68回日本応用物理学会学術講演会
    • Place of Presentation
      北海道
    • Year and Date
      20070904-08
  • [Presentation] c-Ab1, a tyrosine kinase involved in chronic myeloid leukemia, regulates nucleo-cytoplasmic shuttling of DGKαand cell cycle2007

    • Author(s)
      Shirai,Y., Matsubara,T., Saito, N.
    • Organizer
      FASEB Summer Research Conferences
    • Place of Presentation
      Indian Wells CA
    • Year and Date
      20070811-16
  • [Presentation] A regulated adaptor function of p40phox : Intramolecular interaction (PX-PB1 domain)within p40phox2007

    • Author(s)
      Ueyama,T., Tatsuno,T., Kawasaki,T., Thomas L.Leto., Saito, N.
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      ロードアイランド
    • Year and Date
      20070610-15
  • [Presentation] 核内脂質シグナル及び核移行蛋白質の可視化システムを用いた細胞周期機構の解明-DGK の核-細胞質間移行機構と核内における機能に着目して-2007

    • Author(s)
      白井康仁、松原岳大、齋藤尚亮
    • Organizer
      第49回日本脂質生化学会
    • Place of Presentation
      北海道
    • Year and Date
      20070605-06
  • [Presentation] D核内脂質シグナル及び核移行蛋白質の可視化システムを用いた細胞周期機構の解明-DGKの核-細胞質間移行機構と核内における機能に着目して2007

    • Author(s)
      白井康仁、松原岳大、齋藤尚亮
    • Organizer
      第49回日本脂質生化学会
    • Place of Presentation
      北海道
    • Year and Date
      20070605-06
  • [Presentation] DG-PKCシグナル系の可視化とその異常による疾患2007

    • Author(s)
      齋藤尚亮、白井康仁、松原岳大、足立直子、高橋英之、酒井規雄
    • Organizer
      第49回日本脂質生化学会
    • Place of Presentation
      北海道
    • Year and Date
      20070605-06
  • [Presentation] 脊髄小脳失調症14型における変異PKCγのC1Aとキナーゼドメインを介した分子間相互作用・凝集体形成傾向の重要性2007

    • Author(s)
      高橋英之、足立直子、杉本卓弥、中北順也、関貴弘、入江一浩、酒井規雄、齋藤尚亮
    • Organizer
      第112回日本薬理学会近畿部会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2007-11-16
  • [Presentation] ヒトケラチノサイトにおけるTNF-αによるNGF 分泌促進作用とそのシグナル2007

    • Author(s)
      伝達機能, 高岡幸二、白井康仁、齋藤尚亮
    • Organizer
      第111回日本薬理学会近畿部会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-15
  • [Presentation] RalAはηPKCによるケラチノサイトの扁平化に必須である。2006

    • Author(s)
      白井康仁、盛岡祥子、大辻千裕、吉野健一、酒井規雄、上山健彦、齋藤尚亮
    • Organizer
      第113回日本薬理学会近畿部会
    • Place of Presentation
      岡山
    • Year and Date
      2006-06-20
  • [Presentation] P2Y受容体を介するγPKCのオシレーション機構の解明2006

    • Author(s)
      芦田典明、上山健彦、力武恭子、白井康仁、衛藤三佳、近藤威、甲村英二、齋藤尚亮
    • Organizer
      第113回日本薬理学会近畿部会
    • Place of Presentation
      岡山
    • Year and Date
      2006-06-20

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Published: 2010-06-10   Modified: 2016-04-21  

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