Structure and function relationships of the anti -oncogenic START-GAP family gene products

• Project/Area Number: 19570184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: University of Hyogo
• Principal Investigator: HITOSHI Yagisawa University of Hyogo, 大学院・生命理学研究科, 准教授 (40192380)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: シグナル伝達 / 細胞骨格・運動 / 抗がん遺伝子 / 癌 / 細胞内シグナル伝達 / アクチン細胞骨格 / 接着斑 / RhoGAP / 細胞形態 / phopsholipase C / START -GAP / START-GAP

Research Abstract

哺乳動物には、STARTドメインを持つRhoファミリー低分子量Gタンパク質に対するGTPアーゼ活性化タンパク質(START-GAP)をコードする遺伝子が3つ存在し、これらの遺伝子産物の抗腫瘍活性が注目されている。それぞれの生化学・細胞生物学的性質を比較解析したところ、START-GAPの接着斑への局在化が細胞運動性や形態維持に重要な役割を果たしていることが判明した。また、局在化に必要な領域を同定し、その分子機構の一部を解明した。

Research Products

• [Journal Article] Dynamin 2 is required for actin assembly in phagocytosis in Sertoli cells (2009)
  • Author(s): Otsuka, A., Abe, T., Watanabe, M., Yagisawa, H., Takei, K. and Yamada, H.
  • Journal Title: Biochem Biophys Res Commun 378 Pages: 478-482
  • Peer Reviewed
• [Journal Article] Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and morphology (2009)
  • Author(s): Kawai, K., Iwamae, Y., Yamaga, M., Ishii, H., Hirata, H., Homma, Y. and Yagisawa, H.
  • Journal Title: Genes Cells 14 Pages: 227-241
  • Peer Reviewed
• [Journal Article] START-GAP2/DLC2 is localized in focal adhesions via its N-terminal region (2009)
  • Author(s): Kawai, K., Seike, J., Iino, T., Kiyota, M., Iwamae, Y. and Yagisawa, H.
  • Journal Title: Biochem. Biophys. Res. Commun 380 Pages: 736-741
  • Peer Reviewed
• [Journal Article] Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and morphology (2009)
  • Author(s): Kawai, et al.
  • Journal Title: Genes Cells 14 Pages: 227-241
  • Peer Reviewed
• [Journal Article] START-GAP2/DLC2 is localized in focal adhesions via its N-terminal region (2009)
  • Author(s): Kawai, el at.
  • Journal Title: Biochem. Biophys. Res. Commun 380 Pages: 736-741
  • Peer Reviewed
• [Journal Article] Recruitment and activation of phospholipase C (PLC)-δ_1 in lipid rafts by muscarinic stimulation of PC12 cells : contribution of p122RhoGAP/DLC1, a tumor-suppressing PLCδ_1 binding protein (2008)
  • Author(s): Yamaga, M., Kawai, K., Kiyota, M., Homma Y. and Yagisawa, H.
  • Journal Title: Adv. Enzyme Regul 48 Pages: 41-54
  • Peer Reviewed
• [Journal Article] Recruitment and activation of phospholipase C (PLC)-d_1 in lipid rafts by muscarinic stimulation of PC12 cells : contribution of p122RhoGAP/DLC1, a tumor-suppressing PLCδ_1 binding protein (2008)
  • Author(s): Yamaga M., et al.
  • Journal Title: Adv. Enzyme Regul. 48 Pages: 41-54
  • Peer Reviewed
• [Journal Article] Recruitment and activation of phospholipase C (PLC)-δ_1 in lipid rafts by muscarinic stimulation of PC12 cells: contribution of p122RhoGAP/DLC1, a tumor-suppressing PLCδ_1 binding protein. (2008)
  • Author(s): Yamaga M, et. al.
  • Journal Title: Adv. Enzyme Regulation 48
  • Peer Reviewed
• [Journal Article] Phosphatidylserine induces functional and structural alterations of the membrane-associated PH domain of phospholipase C-δ1 (2007)
  • Author(s): Uekama, N., Sugita, T., Okada, M., Yagisawa, H. and Tuzi, S.
  • Journal Title: FEBS J. 274 Pages: 177-187
  • Peer Reviewed
• [Journal Article] Lipid components in the detergent-resistant membrane microdomain (DRM) obtained from the synaptic plasma membrane of rat brain (2007)
  • Author(s): Matsuura, D., Taguchi, K., Yagisawa, H. and Maekawa S.
  • Journal Title: Neurosci. Lett. 423 Pages: 158-161
  • Peer Reviewed
• [Journal Article] START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology (2007)
  • Author(s): Kawai, K., Kiyota, M., Seike J., Deki, Y. and Yagisawa H.
  • Journal Title: Biochem. Biophys. Res. Commun 364 Pages: 783-789
  • Peer Reviewed
• [Journal Article] START-GAP/DLC3 is a GAP for RhoA and Cdc42 and is localized in forcal adhesions regulating cell morphology. (2007)
  • Author(s): Kawai K, et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 364 Pages: 783-789
  • Peer Reviewed
• [Journal Article] Lipid components in the detergent-resistant membrane microdomain(DRM) obtained from the synaptic plasma membrane of rat brain. (2007)
  • Author(s): Matsuura D, et. al.
  • Journal Title: Neurosci Lett. 423 Pages: 158-161
  • Peer Reviewed
• [Presentation] Influence of membrane curvature on the structure of the phospholipase C (PLC)-δ1 PH domain : implication in intracellular localization (2009)
  • Author(s): Uekama, N., Aoki, T., Muraoka, T., Yagisawa, H., Nishimura K. and Tuzi, S.
  • Organizer: Gordon Research Conference on "Signal Transduction Within the Nucleus."
  • Place of Presentation: California, USA
• [Presentation] Influence of membrane curvature on the structure of the phospholipase C(PLC)-δ1 PH domain : implication in intracellular localization (2009)
  • Author(s): Uekama N., et al.
  • Organizer: Gordon Research Conference on Signal Transduction in the Nucleus.
  • Place of Presentation: California, 米国
• [Presentation] Ca^<2->-dependent nuclear accumulation of phospholipase C-δ1 (2008)
  • Author(s): Yagisawa, H. and Okada, M.
  • Organizer: 第31回神経科学会大会
  • Place of Presentation: 東京
• [Presentation] Measurement of inositol polyphosphates by ion chromatography and their physiological status in higher plants (2008)
  • Author(s): Mimura, T., Mitsuhashi, N., Richardso, A., Chung, S-K. and Yagisawa, H.
  • Organizer: 第31回神経科学会大会
  • Place of Presentation: 東京
• [Presentation] 脂質膜上における局所構造の特徴に基づくpleckstrin homology domain-脂質膜間相互作用の解析 (2008)
  • Author(s): 徳田尚美、八木澤仁、福井泰久、辻暁
  • Organizer: 第47回NMR討論会
  • Place of Presentation: 筑波
• [Presentation] イノシトールリン脂質代謝酵素の核-細胞質間移行とその生理的意義BMB2008 (2008)
  • Author(s): 八木澤仁
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム「核-細胞質間輸送と生命機能制御のインターフェイス」
  • Place of Presentation: 神戸
• [Presentation] START-GAP1の接着斑局在化におけるテンシン2との結合の役割 (2008)
  • Author(s): 北村真也、前平航司、川合克久、西谷秀男、八木澤仁
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] START-GAP1は接着斑局在化領域のテンシン2に対するリン酸化依存的結合により接着斑に局在化する (2008)
  • Author(s): 川合克久、北村真也、川合由華、西谷秀男、八木澤仁
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Ca^(2+)-dependent nuclear accumulation of phospholipase Cδ1 (2008)
  • Author(s): 八木澤仁, 岡田雅司
  • Organizer: 第31回神経科学会大会
  • Place of Presentation: 東京
• [Presentation] Measurement of inositol polyphosphates by ion chromatography and their physiological status in higher plants. (2008)
  • Author(s): 三村徹郎, 八木渾仁, 他
  • Organizer: 第31回神経科学会大会
  • Place of Presentation: 東京
• [Presentation] 脂質膜上における局所構造の特徴に基づくpleckstrin homology domain-脂質膜間相互作用の解析 (2008)
  • Author(s): 徳田尚美, 八木澤仁, 他
  • Organizer: NMR討論会
  • Place of Presentation: 筑波
• [Presentation] イノシトールリン脂質代謝酵素の核-細胞質間移行とその生理的意義 (2008)
  • Author(s): 八木澤 仁
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] START-GAP1の接着斑局在化におけるテンシン2との結合の役割 (2008)
  • Author(s): 北村真也, 他 八木澤仁
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] START-GAP1は接着斑局在化領域のテンシン2に対するリン酸化依存的結合により接着斑に局在化する. (2008)
  • Author(s): 川合克久, 他 八木澤仁
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Regulation of intercellular lacalization of a dual functional PLCδ1-binding protein,p122 RhoGAP/DLC1,a member of the tumor-suppressing STA RT-GAP Family proteins. (2007)
  • Author(s): Yagisawa H, et. al.
  • Organizer: 48^<th> International Symposium on "Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues
  • Place of Presentation: University of Bologna, Italy.
  • Year and Date: 2007-09-24
• [Presentation] 固体NMRによる膜表在性タンパク質PLC-δ1PHドメインの局所運動性解析 (2007)
  • Author(s): 上釜奈緒子、八木澤仁、辻暁、西村勝之
  • Organizer: 第46回NMR討論会
  • Place of Presentation: 札幌
• [Presentation] Regulation of intracellular localization of a dual functional PLCδ1-binding protein, p122RhoGAP/DLC1, a member of the tumor suppressing START-GAP family proteins (2007)
  • Author(s): Yagisawa, H., Kawai, K., Iwamae, Y., Kiyota, M. and Yamaga, M.
  • Organizer: 48^<th> International Symposium on "Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues
  • Place of Presentation: Bologna, Italy
• [Presentation] Phosphorylation of phospholipase C-δ_1 regulates its enzymatic activity (2007)
  • Author(s): Fujii, M. and Yagisawa, H.
  • Organizer: Howard Hughes Medical Institute, Janelia Conference on "Inositide Signalling"
  • Place of Presentation: Virginia USA
• [Presentation] START-GAP1, a PLCδ_1-binding RhoGAP, in focal adhesions regulates cell morphology and motility (2007)
  • Author(s): Yagisawa, H., Seike, J., and Kawai, K.
  • Organizer: Howard Hughes Medical Institute, Janelia Conference on "Inositide Signalling"
  • Place of Presentation: Virginia USA
• [Presentation] 脂質二重膜表面の曲率とホスホリパーゼC-δ1 PH ドメインの立体構造変化 : 固体NMR分光法による解析 (2007)
  • Author(s): 上釜奈緒子、青木隆広、丸岡俊宏、栗栖聖治、畠山明子、岡田雅司、八木澤仁、西村勝之、辻暁
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会合同大会)
  • Place of Presentation: 横浜
• [Presentation] p122RhoGAPによる細胞形態変化には接着斑への局在化が寄与する (2007)
  • Author(s): 川合克久、清田稔、清家淳一、岩前由衣、八木澤仁
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会)
  • Place of Presentation: 横浜
• [Presentation] 固体NMR分光法による膜表在性タンパク質PLC-δ1の局所運動性の解析 (2007)
  • Author(s): 上釜奈緒子、八木澤仁、辻暁、西村勝之
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
• [Presentation] ホスホリパーゼC-δ1PHドメインおよびEF-handドメインの脂質二重膜上における構造とダイナミクス (2007)
  • Author(s): 三宅健史、川合克久、八木澤仁、辻暁
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
• [Presentation] 脂質二重膜表面におけるpleckstrin homology domain の動的構造の解析 (2007)
  • Author(s): 徳田尚美、八木澤仁、福井泰久、辻暁
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
• [Presentation] 固体NMRによる膜表在性タンパク質PLC-δ1PHドメインの局所運動性解析。 (2007)
  • Author(s): 上釜 奈緒子, 他
  • Organizer: 第46回NMR討論会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] Study of Local Mobility of Lipids and Membrane Bound Protein by Solid State NMR. (2007)
  • Author(s): Nishimura K, et. al.
  • Organizer: The 16^<th> International Society of Magnetic Reso nance(ISMAR)
  • Place of Presentation: Kenting TAIWAN
• [Presentation] Phosphorylation of phospholipase C-deltal regulates its enzymatic activity. (2007)
  • Author(s): Fujii M, et. al.
  • Organizer: Howard Hughes Medical Institute, Janelia Conference"Inositide Signalling,"
  • Place of Presentation: Virginia USA
• [Presentation] START-GAPI,a PLCdeltal-binding RhoGAP,in focal adhesions regul ates cell morphology and motility, (2007)
  • Author(s): Yagisawa H, et. al.
  • Organizer: Howard Hughes Medical Institute, Janelia Conference"Inositide Signalling, "
  • Place of Presentation: Virginia USA
• [Presentation] 脂質二重膜表面の曲率とホスホリパーゼC-δ1 PHドメインの立体構造変化:固体NMR分光法による解析。 (2007)
  • Author(s): 上釜 奈緒子, 他
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会合同大会)
  • Place of Presentation: パシフィコ横浜
• [Presentation] p122RhoGAPによる細胞形態変化には接着斑への局在化が寄与する。 (2007)
  • Author(s): 川合 克久, 他
  • Organizer: BMB2007(第30回日本分子生物学会年会・第80回日本生化学会合同大会)
  • Place of Presentation: パシフィコ横浜
• [Presentation] Study of Local Mobility of Peripheral membrane protein PLC-δl by solid state NMR. (2007)
  • Author(s): Uekama N, et. al.
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] StUdy of Local Mobility of Peripheral membrane protein PLC-δl by solid state NMR. (2007)
  • Author(s): Uekama N, et. al.
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Spectroscopic study of the structure and dynamics of pleckstr in homology domain at the lipid bilayer surface. (2007)
  • Author(s): Tokuda N, et. al.
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: パシフィコ横浜
• [Book] Phosphoinositide-specific phospholipase C : Isoforms and related molecules (2009)
  • Author(s): Yagisawa, H.
  • Publisher: Berlin Heidelberg(In "Handbook of Neurochemistry and Molecular Neurobiology (3^<rd> Edition), Neural Signal Mechanism Vol. 1b (ed. Mikoshiba K.), Chapter 14 : Phospholipid signaling and cell function, Springer-Verlag)
• [Book] Handbook of Neurochemistry and Molecular Neurobiology (3^<rd> Edition), Neural Signal Mechanism Vol. 1b (ed. Mikoshiba K. ), Chapter 14 : Phospholipid signaling and cell function. Springer, New York. (2009)
  • Author(s): Yagisawa H., et al.
  • Publisher: Phosphoinositide-Specific phospholipase C : Isoforms and related molecules.
• [Book] Handbook of Neurochemistry and Molecular Neurobiology(3^<rd> Edition), Neural Signal Mechanism Vol.1b(ed.Mikoshiba K.), Chapter 20:Phospholipid signaling and cell function.Springer, New York. (2008)
  • Author(s): Yagisawa H, et. al.
  • Total Pages: 28
  • Publisher: Phosphoinositide-specific phospholipase C:Isoforms and related molecules.
• [Remarks]
  • URL: http://www.sci.u-hyogo.ac.jp/life/biosig/kenkyu.html
• [Remarks]
  • URL: http://www.sci.u-hyogo.ac.jp/life/biosig/index.html