Identification and characterization of a novel target for CaM-kinase cascade

• Project/Area Number: 19570134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kagawa University
• Principal Investigator: TOKUMITSU Hiroshi Kagawa University, 医学部, 准教授 (20237077)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Ryoji 香川大学, 医学部, 教授 (00020917) ; 波多野 直哉 香川大学, 希少糖研究センター, 客員准教授 (10332280)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: CaM-キナーゼカスケード / 細胞内カルシウム / CaMKKCaM-KIV / SAD-キナーゼ / タンパク質リン酸化反応 / シグナル伝達 / カルモデュリン / CaMKK / CaM-KIV

Research Abstract

機能プロテオミクス法によりCaM-キナーゼの新規標的リン酸化酵素を探索した。その結果、神経特異的リン酸化酵素であるSAD-キナーゼがCaMKKの標的酵素であることを見いだした。試験管内においてSAD-キナーゼはCaMKKによってそのThr189がリン酸化されることにより、約60倍の活性化を示した。このSAD-キナーゼの活性化は培養細胞系においても確認され、CaMKK/SAD-キナーゼという新しい細胞内カルシウムシグナル伝達経路が示唆された

Research Products

• [Journal Article] Breast cancer cells with stem cell-type markers (CD44+ CD24lo ) are eliminated by Notch and Numb peptide -activated T cells (2009)
  • Author(s): Mine T, Matsueda S, Tokumitsu H, Gao H, Danes C, and Ioannides C.G.
  • Journal Title: Cancer Immunology Immunotherapy (掲載確定)
  • Peer Reviewed
• [Journal Article] Breast Cancer cells with stem cell-type markers (CD44+ CD241o) are eliminated by Notch and Numb peptide-activated T cells (2009)
  • Author(s): T. Mine, et al.
  • Journal Title: Cancer Immunology Immunotherapy (未定)(掲載確定)
  • Peer Reviewed
• [Journal Article] Activation of SAD Kinase by Ca2+/Calmodulin-dependent Protein Kinase Kinase (2008)
  • Author(s): Fujimoto T, Yurimoto S, Hatano N, Nozaki N, Sueyoshi N, Kameshita I, Mizutani A, Mikoshiba K, Kobayashi R, and Tokumitsu H
  • Journal Title: Biochemistry 47(13) Pages: 4151-4159
  • Peer Reviewed
• [Journal Article] Calmodulin-kinases (2008)
  • Author(s): Wayman G. A., Lee Y-S., Tokumitsu H, Silva A, and Soderling T. R.
  • Journal Title: Modulators of Neuronal Development and Plasticity Neuron 59(6) Pages: 914-931
  • Peer Reviewed
• [Journal Article] Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins Hsp90/Hsp70-organizing protein and kinesin-light chain (2008)
  • Author(s): Shimamoto S, Takata M, Tokuta M, Oohira F, Tokumitsu H, and Kobayashi R
  • Journal Title: Journal of Biological Chemistry 83(42) Pages: 28246-28258
  • Peer Reviewed
• [Journal Article] The Role of Calcium/Calmodulin-Dependent Protein Kinase Cascade on MIP-1a Gene Expression of ATL Cells (2008)
  • Author(s): Matsumoto K, Murao K, Imachi H, Nishiuchi T, Cao W M, Yu X, Li J, Ahmed R A M, Iwama H, Tokumitsu H, and Ishida T
  • Journal Title: Experimental Hematology 36(4) Pages: 390-400
  • Peer Reviewed
• [Journal Article] 14-3-3 proteins directly regulate Ca2+/calmodulin-dependent protein kinase kinaseαthrough phosphorylation- dependent multisite binding (2008)
  • Author(s): Ichimura T, Taoka M, Hozumi Y, Goto K, and Tokumitsu H
  • Journal Title: FEBS Letters 582(5) Pages: 661-665
  • Peer Reviewed
• [Journal Article] The Role of Calcium/Calmodulin-Dependent Protein Kinase Cascade on MIP-1α Gene Expression of ATL Cells (2008)
  • Author(s): K. Matsumoto, et al.
  • Journal Title: Experimental Hematology 36 Pages: 390-400
  • Peer Reviewed
• [Journal Article] 14-3-3 proteins directly regulate Ca^<2+>/calmodulin-dependent protein kinase kinase α through phosphorylation-dependent multisite binding (2008)
  • Author(s): T. Ichimura, et al.
  • Journal Title: FEBS Letters 582 Pages: 661-665
  • Peer Reviewed
• [Journal Article] Activation of SAD Kinase by Ca^<2+>/Calmodulin-dependent Protein Kinase Kinase (2008)
  • Author(s): T. Fujimoto, et al.
  • Journal Title: Biochemistry 47 Pages: 914-931
  • Peer Reviewed
• [Journal Article] Calmodulin-kinases ; Modulators of Neuronal Developement and Plasticity (2008)
  • Author(s): G A. Wayman, et al.
  • Journal Title: Neuron 59 Pages: 914-931
  • Peer Reviewed
• [Journal Article] Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain (2008)
  • Author(s): S. Shimamoto, et at.
  • Journal Title: Journal of Biological Chemistry 83 Pages: 28246-28258
  • Peer Reviewed
• [Journal Article] 14-3-3 proteins directly regulate Ca^<2+>/calmodulin-dependent protein kinase kinaseαthrough phosphorylation-dependent multisite binding (2008)
  • Author(s): T. Ichimura, et. al.
  • Journal Title: FEBS Letters 582 Pages: 661-665
  • Peer Reviewed
• [Journal Article] Distinct developmental expression of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases (2007)
  • Author(s): Kamata A, Sakagami H, Tokumitsu H, Sanda M, Owada Y, Fukunaga K, and Kondo H
  • Journal Title: Neuroscience Letters 423(2) Pages: 143-148
  • Peer Reviewed
• [Journal Article] Distinct developmental expression of two isoforms of Ca^<2+>/calmodulin-dependentprotein kinase kinases and their involvement in hippocampal dendritic formation (2007)
  • Author(s): A. Kamata, et. al.
  • Journal Title: Neuroscience Letters 432 Pages: 143-148
  • Peer Reviewed
• [Journal Article] Knockdown of nuclear Ca^<2+>/calmodulin-dependent protein kinase phosphatase causes developmental abnormalities in zebrafish (2007)
  • Author(s): T. Nimura, et. al.
  • Journal Title: Archives of Biochemistry and Biophysics 457 Pages: 205-216
  • Peer Reviewed
• [Journal Article] Spatiotemporal expression of four isoforms of Ca^<2+>/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth (2007)
  • Author(s): A. Kamata, et. al.
  • Journal Title: Neuroscience Research 57 Pages: 86-97
  • Peer Reviewed
• [Presentation] 機能プロテオミクス法を用いたカルモデュリン結合タンパク質の網羅的探索 (2008)
  • Author(s): 揺本-横倉沙紀
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins (2008)
  • Author(s): 高田麻紀
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] カルモデュリン・キナーゼIアイソフォームの活性化機構の解析 (2008)
  • Author(s): 藤本智仁
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会
• [Presentation] 機能的プロテオミクス法を用いたカルモデュリン結合タンパク質の網羅的探索 (2008)
  • Author(s): 揺本-横倉沙紀
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70- organizig protein and kinesin-light chain (2008)
  • Author(s): 高田麻紀
  • Organizer: 第31回日本分子生物学会第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] ユビキチンリガーゼCHIPのCa2+結合タンパク質S100による調節 (2008)
  • Author(s): 嶋本聖子
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] SAD-BのCaM-KKによるリン酸化と活性化 (2007)
  • Author(s): 藤本智仁
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] S100タンパク質によるHsp70/Hsp90分子シャペロン複合体の形成調節 (2007)
  • Author(s): 嶋本聖子
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Kinesin light chain (KLC)とKLC結合蛋白質の相互作用に対するS100蛋白質の影響について (2007)
  • Author(s): 高田麻紀
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] S100タンパク質によるImmunophilin/Hsp90複合体の形成調節 (2007)
  • Author(s): 小池 克英
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Kinesin light chain(KLC)とKLC結合蛋白質の相互作用に対するS100蛋白質の影響について (2007)
  • Author(s): 高田 麻紀
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会
  • Place of Presentation: 横浜