Phosphorylation-dependent regulatory mechanism of calmoudlin-kinase cascade

• Project/Area Number: 26440056
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Okayama University
• Principal Investigator: Tokumitsu Hiroshi 岡山大学, 自然科学研究科, 教授 (20237077)
• Co-Investigator(Kenkyū-buntansha): 曲 正樹 岡山大学, 自然科学研究科, 助教 (50359882)
• Co-Investigator(Renkei-kenkyūsha): HATANO Naoya 神戸大学, 大学院医学(系)研究科, 特命助教 (10332280)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: CaMKK / AMPK / STO-609 / CaMK cascade / Protein Kinase / Signal Transduction / リン酸化反応 / AMPキナーゼ / CaMキナーゼI V / 細胞内カルシウム / シグナル伝達 / 特異性 / CaMK Cascade

Outline of Final Research Achievements

Intracellular Ca2+ plays an important role in the cellular signal transduction system as a second messenger. Calmodulin (caM) is one of Ca2+-binding proteins, which activates multifunctional CaM-kinases. In this research, we examined the molecular mechanism of substrate recognition for Ca2+/calmodulin-dependent protein kinase kinase beta based on the structure-function analysis.

Research Products

• [Int'l Joint Research] University of Southern California/Keck School of Medicine(米国)
• [Journal Article] Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms. (2016)
  • Author(s): Yuya Fujiwara, Yoshinori Kawaguchi, Tomohito Fujimoto, Naoki Kanayama, Masaki Magari, Hiroshi Tokumitsu
  • Journal Title: The Journal of biological chemistry Volume: 291 Issue: 26 Pages: 13802-13808
  • DOI: 10.1074/jbc.m116.727867
  • Peer Reviewed
• [Journal Article] Identification of striated muscle activator of Rho signaling (STARS) as a novel calmodulin target by a newly developed genome-wide screen. (2016)
  • Author(s): Yusui Furuya, Miwako Denda, Kyohei Sakane, Tomoko Ogusu, Sumio Takahashi, Masaki Magari, Naoki Kanayama, Ryo Morishita, Hiroshi Tokumitsu
  • Journal Title: Cell calcium Volume: 60 Issue: 1 Pages: 32-40
  • DOI: 10.1016/j.ceca.2016.04.004
  • Peer Reviewed
• [Journal Article] Oxidative Stress Impairs the Stimulatory Effect of S100 Proteins on Protein Phosphatase 5 Activity (2016)
  • Author(s): Yamaguchi F, Tsuchiya M, Shimamoto S, Fujimoto T, Tokumitsu H, Tokuda M, and Kobayashi R
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 240 Issue: 1 Pages: 67-78
  • DOI: 10.1620/tjem.240.67
  • NAID: 130006776928
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Analysis of Distinct Roles of CaMKK Isoforms using STO-609-Resistant Mutants in Living Cells. (2015)
  • Author(s): Fujiwara Y, Hiraoka Y, Fujimoto T, Kanayama N, Magari M, Tokumitsu H.
  • Journal Title: Biochemistry Volume: 54 Issue: 25 Pages: 3969-3977
  • DOI: 10.1021/acs.biochem.5b00149
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. (2015)
  • Author(s): Siddique HR, Feldman DE, Chen CL, Punj V, Tokumitsu H, Machida K.
  • Journal Title: Hepatology Volume: 62 Issue: 5 Pages: 1466-1479
  • DOI: 10.1002/hep.27987
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators (2015)
  • Author(s): Miyamoto T, Rho E, Sample V, Akano H, Magari M, Ueno T, Gorshkov K, Chen M, Tokumitsu H, Zhang J, Inoue T
  • Journal Title: Cell Reports Volume: 印刷中 Issue: 4 Pages: 657-670
  • DOI: 10.1016/j.celrep.2015.03.057
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN‑45 gastric carcinoma cells (2014)
  • Author(s): Tsuchiya M, Yamaguchi F, Shimamoto S, Fujimoto T, Tokumitsu H, Tokuda M, Kobayashi R
  • Journal Title: International Journal of Molecular Medicine Volume: 34 Issue: 6 Pages: 1713-1719
  • DOI: 10.3892/ijmm.2014.1947
  • Peer Reviewed
• [Presentation] Ca2+/Calmodulin-dependent Protein Kinase Kinaseシグナル伝達機構の茶道原理の解明（基質認識機構） (2016)
  • Author(s): 藤原侑哉、川口義典、藤本智仁、金山直樹、曲正樹、徳光 浩
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Calmodulin Signal Networkのインターラクトーム解析 (2015)
  • Author(s): 徳光 浩
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] CaMKKβによる選択的AMPK活性化の細胞生物学的および生化学的解析 (2015)
  • Author(s): 藤原 侑哉、川口 義典、藤本 智仁、曲 正樹、金山 直樹、徳光 浩
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Ca2+/Calmodulin結合型転写因子の網羅的同定 (2015)
  • Author(s): 太尾田 泰成、大西 和貴、古谷 雄穂、傳田 美和子、金山 直樹、曲 正樹、森下 了、徳光 浩
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] COMPREHENSIVE IDENTIFICATION OF HUMAN CALMODULIN-TARGETS (2015)
  • Author(s): Furuya Y, Denda M, Kanayama N, Magari M, Morishita R, Tokumitsu H
  • Organizer: 19th International Symposium on Calcium Binding Proteins and Calcium Function In Health and Disease
  • Place of Presentation: ナッシュビル・アメリカ
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] ANALYSIS OF DISTINCT ROLES OF CAMKK ISOFORMS USING STO-609- RESISTANT MUTANTS IN LIVING CELLS (2015)
  • Author(s): Fujiwara Y, Hiraoka Y, Fujimoto T, Kanayama N, Magari M, Tokumitsu H
  • Organizer: 19th International Symposium on Calcium Binding Proteins and Calcium Function In Health and Disease
  • Place of Presentation: ナッシュビル・アメリカ
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] ヒトCalmodulin標的分子の網羅的同定 (2014)
  • Author(s): 古谷 雄穂, 西口 みゆ, 傳田美和子, 曲 正樹，金山 直樹，森下 了, 徳光 浩
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
• [Presentation] STO-609抵抗性変異体を用いたCaMKKシグナル伝達の機能解析 (2014)
  • Author(s): 藤原 侑哉, 平岡 佑理, 曲 正樹，金山 直樹，徳光 浩
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-17
• [Presentation] カルモデュリン標的分子の網羅解析から見た カルシウムシグナル伝達の多様性 (2014)
  • Author(s): 徳光 浩
  • Organizer: 日本薬学会関東支部会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-04
  • Invited
• [Remarks] 岡山大学・大学院自然科学研究科 細胞機能設計学研究室ホームページ
  • URL: http://www.okayama-u.ac.jp/user/saibou/index.html
• [Remarks] 岡山大学 研究者総覧
  • URL: http://soran.cc.okayama-u.ac.jp/view?l=ja&u=a94ada4de7b2082d74506e4da22f6611