Integration and regulatory mechanism for growth factor and cell adhesion signals

• Project/Area Number: 23570227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: MIZUSHIMA Hiroto 大阪大学, 微生物病研究所, 助教 (30379094)
• Co-Investigator(Renkei-kenkyūsha): MEKADA Eisuke 大阪大学, 微生物病研究所, 教授 (20135742)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 増殖因子 / 細胞接着 / 細胞増殖 / 細胞骨格

Outline of Final Research Achievements

To elucidate regulatory mechanism for integration of growth factor signal and cell adhesion signal, role of FAK, which is a common downstream signaling molecule of EGFR and integrin, and its regulatory mechanisms were examined. As a result, FAK was found out to be required for EGFR-dependent cell growth. Furthermore, a FAK mutant carrying phosphorylation-mimic mutation at FERM domain inhibited cell growth by interacting with microtubules through chaperones. Taken together these results, it was suggested that FAK could positively and negatively regulate cell growth depending on phosphorylation states of FERM domain.

Research Products

• [Journal Article] Identification of diphtheria toxin R domain mutants with enhanced inhibitory activity against HB-EGF (2015)
  • Author(s): Suzuki K, Mizushima H, Abe H, Iwamoto R, Nakamura H, Mekada E
  • Journal Title: J Biochem Volume: mvu079 Issue: 5 Pages: 331-343
  • DOI: 10.1093/jb/mvu079
  • NAID: 40020461422
  • Peer Reviewed / Open Access
• [Journal Article] HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers (2011)
  • Author(s): Murata T, Mizushima H, Chinen I, Moribe H, Yagi S, Hoffman RM, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E.
  • Journal Title: Cancer Res. Volume: 71 (21) Pages: 6633-6642
  • Peer Reviewed
• [Presentation] FAKリン酸化によるHB-EGF依存的細胞増殖制御 (2014)
  • Author(s): 水島寛人、船越敍希、目加田英輔
  • Organizer: 第６６回日本細胞生物学会大会
  • Place of Presentation: 奈良県新公会堂
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] Sequestration of FAK on microtubule negatively regulates HB-EGF-dependent cell growth (2013)
  • Author(s): Hiroto Mizushima, Mitsuki Funakoshi, Eisuke Mekada
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: ウインクあいち（愛知県産業労働センター）
• [Presentation] HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-Associated Fibroblasts to Support Progression of Uterine Cervical Cancers (2012)
  • Author(s): Hiroto Mizushima, Takuya Murata, Ichino Chinen, Hiroki Moribe, Shigeo Yagi, Robert M Hoffman, Tadashi Kimura, Kiyoshi Yoshino, Yutaka Ueda, Takayuki Enomoto, Eisuke Mekada
  • Organizer: 第４５回日本発生学会、第６４回日本細胞生物学会合同大会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Regulation of HB-EGF-dependent cell growth by phosphorylation of FERM domain of FAK
  • Author(s): Hiroto Mizushima, Mitsuki Funakoshi, Eisuke Mekada
  • Organizer: 第６３回日本細胞生物学会大会
  • Place of Presentation: 北海道大学クラーク会館、学術交流会館（北海道）
• [Remarks] 大阪大学微生物病研究所
  • URL: http://www.biken.osaka-u.ac.jp/index.php
• [Remarks] 大阪大学微生物病研究所細胞機能分野
  • URL: http://cell-biology.biken.osaka-u.ac.jp/MekadaLabHP/Home.html