Protein kinases ROCK -Developments of isoform-specific inhibitors and a method to detect active ROCK isoforms

• Project/Area Number: 25440091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Yoneda Atsuko 東京薬科大学, 生命科学部, 助教 (80590372)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 蛋白質リン酸化酵素 / ROCK / がん / 細胞骨格 / 細胞運動 / 細胞外マトリクス

Outline of Final Research Achievements

Specific functions of two homologous protein kinases ROCK in tumor progression was needed to be revealed. This study found that a peptide derived from a ROCK2 specific endogenous inhibitor, CRMP2L, alone is capable of inhibiting cell migration and invasion of colon carcinoma cells, and that GSK3 phosphorylation of CRMP2L regulates inhibition of ROCK-dependent colon carcinoma cell migration/invasion by CRMP2L.

Research Products

• [Journal Article] Syndecan Heparan Sulfate Proteoglycans: Regulation, Signaling and Impact on Tumor Biology. (2015)
  • Author(s): Angelica Maciel Gomes; Dovile Sinkeviciute; Hinke A. B. Multhaupt; Atsuko Yoneda; and John R. Couchman
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 4
  • NAID: 130005265222
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fibronectin Matrix Assembly and Its Significant Role in Cancer Progression and Treatment (2015)
  • Author(s): Yoneda A
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 27 Pages: 1-10
  • NAID: 130005072347
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phosphorylation and mRNA splicing of collapsin response mediator protein-2 determine inhibition of rho-associated protein kinase (ROCK) II function in carcinoma cell migration and invasion (2013)
  • Author(s): Morgan-Fisher M, Couchman JR, Yoneda A
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 43 Pages: 31229-31240
  • DOI: 10.1074/jbc.m113.505602
  • Peer Reviewed
• [Presentation] GSK3 Phosphorylation and mRNA Splicing of Collapsin Response Mediator Protein-2 Control ROCK II-dependent Carcinoma Cell Migration and Invasion (2015)
  • Author(s): Atsuko Yoneda, Marie Morgan-Fisher, Kiyoko Fukami, and John R. Couchman
  • Organizer: 9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Phosphorylation and mRNA Splicing of Collapsin Response Mediator Protein-2 Determine Inhibition of Rho-associated Protein Kinase (ROCK) II Function in Carcinoma Cell Migration and Invasion (2015)
  • Author(s): Atsuko Yoneda, Marie Morgan-Fisher, John R. Couchman, and Kiyoko Fukami
  • Organizer: 第６７回 日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] プロテインキナーゼ ROCK の活性制御による癌細胞の遊走と細胞外マトリックス形成の阻害 (2014)
  • Author(s): 米田敦子
  • Organizer: 第２回 MatriCell フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-09-06 – 2014-09-07
  • Invited
• [Presentation] Fine regulation of common players in cancer cell migration and fibronectin matrix assembly (2013)
  • Author(s): A. Yoneda, M. Morgan-Fisher, A. M. Hoye, U. M. Wewer, and K. Fukami
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 細胞外マトリックスと細胞内アクチン骨格とのインテグリンを介した双方向クロストーク (2013)
  • Author(s): 米田 敦子、M. Morgan-Fisher, A. M. Hoye, U. M. Wewer, J. R. Couchman, 深見 希代子
  • Organizer: 第４５回日本結合組織学会学術大会 第60回マトリックス研究会大会 合同学術大会
  • Place of Presentation: 和歌山
  • Invited
• [Presentation] Fine tuning of ROCK-II function is facilitated by modification of CRMP-2-mRNA splicing, and phosphorylation by GSK-3. (2013)
  • Author(s): M. Morgan-Fisher, J. R. Couchman, U. M. Wewer and A. Yoneda
  • Organizer: Cancer Biology, BRIC 10-year anniversary symposium
  • Place of Presentation: コペンハーゲン、デンマーク