Mechanism of nitric oxide-mediated regulation of non-receptor tyrosine kinases

• Project/Area Number: 19590302
• 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: HAMAGUCHI Michinari Nagoya University, 大学院・医学系・研究科, 教授 (90135351)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 一酸化窒素 / チロシンキナーゼ / Src / レドックス / シグナル伝達 / シグナル伝達系 / Srcキナーゼ / 細胞運動

Research Abstract

一酸化窒素は多くの蛋白の活性を制御し、様々な生理的役割を担っている。我々は非受容体型チロシンキナーゼが、一酸化窒素によるニトロソ化により、活性が制御されることを見出した。Src, FAKは一酸化窒素により活性化されるが、その活性化には保存されたシステインのニトロソ化が重要であった。このニトロソ化による活性化は細胞間接着の制御や、癌細胞の浸潤、転移に関わっていることを明らかにした。

Research Products

• [Journal Article] A role for AP-1 in matrix metalloproteinase production and invadopodia formation of v-Crk-transformed cells (2009)
  • Author(s): Hasegawa H, Senga T, Ito S, Iwamoto T, Hamaguchi M.
  • Journal Title: Exp Cell Res. (in press)
• [Journal Article] A role for AP-1 in matrix metalloproteinase production and invadopodia formation of v-Crk-transformed cells (2009)
  • Author(s): Hasegawa H, Senga T, Ito S, Iwamoto T, Hamaguchi M.
  • Journal Title: Experimental Cell Research (In press)
  • Peer Reviewed
• [Journal Article] The cysteine-cluster motif of c-Yes, Lyn and FAK as a suppressive module for the kinases (2008)
  • Author(s): Rahman MA, Senga T, Oo ML, Hasegawa H, Biswas MH, Mon NN, Huang P, Ito S, Yamamoto T, Hamaguchi M
  • Journal Title: Oncol Rep. 19(4) Pages: 975-80
• [Journal Article] The cysteine-cluster motif of c-Src: its role for the heavy metal mediated activation of kinase (2008)
  • Author(s): Senga T, Hasegawa H, Tanaka M, Rahman MA, Ito S, Hamaguchi M.
  • Journal Title: Cancer Sci. 99(3) Pages: 571-5
  • NAID: 10024003922
• [Journal Article] The cysteine-cluster motif of c-Src : its role for the heavy metal-mediated activation of kinase. (2008)
  • Author(s): Senga T, Hasegawa H, Tanaka, M, Rahman MA, Ito S, Hamaguchi M.
  • Journal Title: Cancer Science 99 Pages: 571-575
  • NAID: 10024003922
  • Peer Reviewed
• [Journal Article] The cysteine-cluster motif of c-Yes, Lyn and FAK as a suppressive module for the kinases. (2008)
  • Author(s): Rahman MA, Senga T, Oo ML, Hasegawa H, Biswas MH, Mon NN, Huang P, Ito S, Yamamoto T, Hamaguchi M.
  • Journal Title: Oncology Reports 19 Pages: 975-980
  • Peer Reviewed
• [Journal Article] A role for SHPS-1/SIRPalpha in Concanavalin A-dependent production of MMP-9 (2007)
  • Author(s): Ruhul Amin AR, Uddin Biswas MH, Senga T, Feng GS, Kannagi R, Agarwal ML, Hamaguchi M.
  • Journal Title: Genes Cells. 12(9) Pages: 1023-33
• [Journal Article] A novel role of phospho-β-catenin in microtubule regrowth at centrosome (2007)
  • Author(s): P. Huang, M. Hamaguchi, et. al.
  • Journal Title: Oncogene 26 Pages: 4357-4371
  • Peer Reviewed
• [Journal Article] Effects of SHIP-1 on MMP-2 secretion and invasion of SR3Y1 cells. (2007)
  • Author(s): W. Xing and M. Hamaguchi.
  • Journal Title: Journal of Genetics and Genomics 34(4) Pages: 285-293
  • Peer Reviewed
• [Journal Article] SIRP α1 and SIRP α2: Their Role as Tumor Suppressors in Breast Carcinoma Cells. (2007)
  • Author(s): Y. Yamasaki, M. Hamaguchi, et. al.
  • Journal Title: Biochem Biophys Res Commun. 361 Pages: 7-13
  • Peer Reviewed
• [Journal Article] A role for SHPS-1/SIRPα in concanavalin A-dependent production of MMP-9. (2007)
  • Author(s): A. R. Amin, M. Hamaguchi, et. al.
  • Journal Title: Genes to Cells 12 Pages: 1023-1033
  • Peer Reviewed
• [Journal Article] Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma. (2007)
  • Author(s): T. Kokuryo, M. Hamaguchi, et. al.
  • Journal Title: Cancer Research 67(20) Pages: 9637-9642
  • Peer Reviewed
• [Presentation] Focal Adhesion Kinase regulates proinflammatory cytokine IL-1beta -dependent MMP-9 production (2008)
  • Author(s): Naing Naig Mon, Satoko Ito, Takeshi Senga, Michinari Hamaguchi
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] NOシグナルと癌の浸潤転移 (2008)
  • Author(s): 千賀威, ラーマンアミナー、浜口道成
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] v-SrcによるヒストンH3のリン酸化はRasシグナルが関与する (2007)
  • Author(s): 丹下正一朗、浜口道成
  • Organizer: 日本分子生物学会、日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Silencing of TLK1 promotes the sensitivity to cisplatin (2007)
  • Author(s): Y. Takayama, M. Hamaguchi, et. al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 癌の浸潤転移とSrc/SHP-2シグナル (2007)
  • Author(s): 浜口道成
  • Organizer: 日本分子生物学会、日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] ギャップ結合機能におけるSHP-2の機能解析 (2007)
  • Author(s): 兵頭寿典、伊藤聡子、千賀威、浜口道成
  • Organizer: 日本分子生物学会、日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] FAK Signaling in Neoplastic Disorder: A Linkage between Inflammation and Cancer (2007)
  • Author(s): M. Hamaguchi
  • Organizer: ISC Conference on Innovative Therapies-New Targets, New Challenges, New Drugs
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2007-11-02
• [Presentation] siRNA-mediated Nek2 depletion leads to inhibition against pancreatic cancer (2007)
  • Author(s): S. Hibino, M. Hamaguchi, et. al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] SHP-2 is critical for invadopodia formation and invasion of Src-transformed cells. (2007)
  • Author(s): S. Senga, M. Hamaguchi, et. al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] v-Crk suppresses the cadherin-catenin cell adhesion system via the Ras-MEK1-MAP kinase pathway (2007)
  • Author(s): S. Ito, M. Hamaguchi, et. al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] POLIM1 is involved in cell spreading and interact with palladin (2007)
  • Author(s): M. Maeda, M. Hamaguchi, et. al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03