Analysis of disease-related genes involved in Rho family small GTPase signaling

• Project/Area Number: 20590308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: AMANO Mutsuki Nagoya University, 医学系研究科, 准教授 (90304170)
• Co-Investigator(Kenkyū-buntansha): KAIBUCHI Kouzou 名古屋大学, 大学院・医学系研究科, 教授 (00169377)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シグナル伝達 / Rhoファミリー / 循環器 / 冠攣縮 / 精神疾患 / キナーゼ / 高血圧 / Rho

Research Abstract

This study aimed to identify and characterize the disease-related genes involved in Rho family small GTPase signaling pathways to understand the pathogenesis of cardiovascular diseases and mental disorders. We found that the SNP (Ala370Ser) within PH domain of ARHGAP9, which is a negative regulator of Rac, was associated with a significant risk of coronary artery spasm. The Ala370Ser polymorphism counteracted ARHGAP9-reduced cell migration, spreading and adhesion, suggesting that it results in a critical difference in ARHGAP9 function.

Research Products

• [Journal Article] Mutation of ARHGAP9 in patients with coronary spastic angina. (2010)
  • Author(s): Takefuji, M., Asano, H., Mori, K., Amano, M., Kato, K., Watanabe, T., Morita, Y., Katsumi, A., Itoh, T., Takenawa, T., Hirashiki, A., Izawa, H., Nagata, K., Hirayama, H., Takatsu, F., Naoe, T., Yokota, M., Kaibuchi, K.
  • Journal Title: Journal of Human Genetics 55 Pages: 42-49
  • NAID: 10030733231
  • Peer Reviewed
• [Journal Article] A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase. (2010)
  • Author(s): Amano, M., Tsumura, Y., Taki, K., Harada, H., Mori, K., Nishioka, T., Kato, K., Suzuki, T., Nishioka, Y., Iwamatsu, A., Kaibuchi, K.
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] Rho-kinase/ROCK : A key regulator of the cytoskeleton and cell polarity. (2010)
  • Author(s): Amano, M., Nakayama, M., Kaibuchi, K.
  • Journal Title: Cytoskeleton 67 Pages: 545-554
  • Peer Reviewed
• [Journal Article] Rho-kinase/ROCK : A key regulator of the cytoskeleton and cell polarity (2010)
  • Author(s): Amano M, et al.
  • Journal Title: Cytoskleleton Volume: 67 Pages: 545-554
  • Peer Reviewed
• [Journal Article] A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase (2010)
  • Author(s): Amano, M., et al.
  • Journal Title: PLoS One 5
  • Peer Reviewed
• [Journal Article] Rho-kinase Contributes to Sustained RhoA Activation through Phosphorylation of p190A RhoGAP. (2009)
  • Author(s): Mori, K., Amano, M., Takefuji, M., Kato, K., Morita, Y., Nishioka, T., Matsuura, Y., Murohara, T., Kaibuchi, K.
  • Journal Title: The Journal of Biological Chemistry 284 Pages: 5067-5076
  • Peer Reviewed
• [Journal Article] Mutation of ARHGAP9 in patients with coronary spastic angina (2009)
  • Author(s): Takefuji, M., et al.
  • Journal Title: J Hum Genet 55 Pages: 42-49
  • Peer Reviewed
• [Journal Article] Rho-kinase contributes to sustained RhoA activation through phosphorylation of p190A RhoGAP. (2009)
  • Author(s): Mori, K., et al.
  • Journal Title: J Biol Chem 284 Pages: 5067-5076
  • Peer Reviewed
• [Journal Article] Prognostic implication and biological roles of RhoH in acute myeloid leukaemia. (2008)
  • Author(s): Iwasaki, T., Katsumi, A., Kiyoi, H., Tanizaki, R., Ishikawa, Y., Ozeki, K., Kobayashi, M., Abe, A., Matsushita, T., Watanabe, T., Amano, M., Kojima, T., Kaibuchi, K., Naoe, T.
  • Journal Title: European Journal of Haematology 81 Pages: 454-460
  • Peer Reviewed
• [Journal Article] Prognostic implication and biological roles of RhoH in acute myeloid leukaemia. (2008)
  • Author(s): Iwasaki, T., et al.
  • Journal Title: Eur J Haematol 81 Pages: 454-460
  • Peer Reviewed
• [Presentation] A proteomic approach for comprehensively screening substrates of proteinkinases (2010)
  • Author(s): Amano M.
  • Organizer: HUPO 2010
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2010-09-20
• [Presentation] 蛋白質問相互作用を利用したキナーゼの新規基質のスクリーニング (2010)
  • Author(s): 天野睦紀
  • Organizer: 第35回日本医用マススペクトル学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-09-10
• [Presentation] A proteomic approach for comprehensively screening substrates of protein kinases. (2010)
  • Author(s): 天野睦紀
  • Organizer: Neuro 2010
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-09-04
• [Presentation] A proteomic approach for comprehensively screening substrates of proteinkinases (2010)
  • Author(s): Amano M.
  • Organizer: Neuro 2010
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-09-04
• [Presentation] Screening of Protein kinase Substrates by an Interactome Approach. (2009)
  • Author(s): 天野睦紀
  • Organizer: Tsuruoka Proteomics Meeting 2009
  • Place of Presentation: Tsuruoka, Japan
  • Year and Date: 2009-12-07
• [Presentation] 蛋白質間相互作用を利用したキナーゼ基質の網羅的解析 (2009)
  • Author(s): 天野睦紀
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-04
• [Presentation] 蛋白質間相互作用を利用したキナーゼ基質の網羅的解析 (2009)
  • Author(s): 天野睦紀
  • Organizer: 第61回 日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-04
• [Presentation] Roles of Rho/Rho-kinase in Cellular functions and Diseases. (2009)
  • Author(s): 天野睦紀
  • Organizer: 10th International Symposium on Mechanisms of Vasodilation
  • Place of Presentation: Matsushima, Japan
  • Year and Date: 2009-06-03
• [Presentation] Roles of Rho/Rho-kinase in Cellular functions and Diseases (2009)
  • Author(s): Mutsuki Amano
  • Organizer: 10th International Symposium on Mechanisms of Vasodilation
  • Place of Presentation: Matsushima, Japan
  • Year and Date: 2009-06-03
• [Presentation] 蛋白質間相互作用を利用したキナーゼ基質の網羅的解析 (2009)
  • Author(s): 天野睦紀
  • Organizer: 第9回日本蛋白質科学会年会
  • Place of Presentation: 熊本
  • Year and Date: 2009-05-21
• [Presentation] Rho-kinasebによるRhoの持続的活性化と血管平滑筋収縮 (2009)
  • Author(s): 天野睦紀
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-18
• [Presentation] Rho-kinaseによるRhoの持続的活性化と血管平滑筋収縮 (2009)
  • Author(s): 天野睦紀
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Rho-kinase and Rho family GTPase signaling. (2008)
  • Author(s): 天野睦紀
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Vermont, USA
  • Year and Date: 2008-07-14
• [Presentation] Rho-kinase and Rho family GTPase signaling (2008)
  • Author(s): Mutsuki Amano
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Vermont, USA
• [Remarks] ホームページ等
  • URL: http://www.med.nagoya-u.ac.jp/Yakuri/
• [Remarks]