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三量体Gタンパク質の脂質ラフト局在と活性調節の分子メカニズムに関する研究

Research Project

Project/Area Number 18057002
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

中畑 則道  Tohoku University, 大学院・薬学研究科, 教授 (60045804)

Co-Investigator(Kenkyū-buntansha) 守屋 孝洋  東北大学, 大学院・薬学研究科, 准教授 (80298207)
小原 祐太郎  東北大学, 大学院・薬学研究科, 助教 (40400270)
斎藤 将樹  東北大学, 大学院・薬学研究科, 助教 (50400271)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2007: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywords脂質ラフト / Gタンパク質 / G_s / サイクリックAMP / Gβ / コレステロール / ガングリオシド / アデニル酸シクラーゼ
Research Abstract

脂質ラフトはスフィンゴ脂質、コレステロールやスフィンゴ糖脂質などに富む細胞膜マイクロドメインであるが、受容体を介するシグナル伝達が効率的に行われる場としても重要であることが近年示唆されている。われわれは最近、PI代謝回転のマストパランによる抑制メカニズムについて検討したところ、マストパランは脂質ラフトからGαqを遊離させ、その作用点は脂質ラフトのガングリオシドであることを明らかにした。しかし、ガングリオシドとGαとの相互作用の分子メカニズムや、Gq以外のGタンパク質の脂質ラフトにおける局在や活性調節におけるガングリオシドの役割については不明のままである。そこで本研究では、マストパランによって引き起こされる脂質ラフトの構成分子の変化を詳細に調べるとともに、Gq以外の三量体Gタンパク質であるGsの局在や活性調節におよぼすマストパランの作用を解析し、脂質ラフトにおける三量体Gタンパク質の活性調節機構の解明を目的とした。はじめにGsの機能について解析を行った。その結果、マストパランはGsシグナルであるサイクリックAMPの上昇作用を用量依存的に抑制し、その作用はガングリオシドによって拮抗されることを明らかにした。また、Gαsの細胞内分布をGFP-Gsを用いて形態的に検討したところ、マストパランはGsを細胞膜から細胞内へと局在変化させることを見出した。一方、脂質ラフト画分を蔗糖密度勾配遠心法により分離すると、正常状態ではGαsが脂質ラフト分画に存在するのに対し、マストパラン処理によりGαsが脂質ラフト分画で減少することが明らかになった。これらの結果から、マストパランのガングリオシドを介する三量体Gタンパク質のラフト局在に及ぼす作用は、GqのみならずGsについても当てはまり、三量体Gタンパク質に共通の現象である可能性が示唆された。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (26 results)

All 2008 2007 2006

All Journal Article (25 results) (of which Peer Reviewed: 3 results) Presentation (1 results)

  • [Journal Article] Type 1 angiotensin receptor (AT1-R)-mediated decrease In type 2 angiotensin receptor mRNA level is dependent on G_q and extracellular signal-regulated kinase 1/2 in AT1-R-transfected PC12 cells2008

    • Author(s)
      Masaki Saito, Yuki Shinohara, Hitomi Sasaki, Yuki Netsu, Makoto Yoshida and Norimichi Nakahata
    • Journal Title

      J. Neuroendocrinol. 20

      Pages: 299-308

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low expression of cell-surface thromboxane A_2 receptor β-isoform through the negative regulation of its membrane traffic by proteasomes2007

    • Author(s)
      Masako Sasaki, Jun Sukegawa, Katsutoshi Miyosawa, Teruyuki Yanagisawa, Satoko Ohkubo and Norimichi Nakahata
    • Journal Title

      Prostagland. Other Lipid Mediat. 83

      Pages: 237-249

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mastoparan inhibits β-adrenoceptor-G_s signaling by changing the localization of Gα_s in lipid rafts2007

    • Author(s)
      Jun Sugama, Jiang-Zhou Yu, Mark M. Rasenick and Norimichi Nakahata
    • Journal Title

      Cell. Signal. 19

      Pages: 2247-2254

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 三量体Gタンパク質を介する情報伝達における脂質ラフトの役割2007

    • Author(s)
      大久保聡子, 中畑則道
    • Journal Title

      薬学雑誌 127

      Pages: 27-40

    • NAID

      110006155007

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct effects of Z-335, a new thromboxane A_2 receptor antagonist, on rabbit platelets and aortic smooth muscles2007

    • Author(s)
      Makoto Yoshida, Yukari Sato, Tokuro Shimura, Satoko Ohkubo, Shigeyoshi Honma, Takao Tanaka, Tadashi Kurimoto, Norimichi Nakahata
    • Journal Title

      Pharmacology 79

      Pages: 50-56

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on the ocular blood flow in rabbits2007

    • Author(s)
      Takashi Konno, Takehiko Uchibori, Akihiko Nagai, Kentaro Kogi, Norimichi Nakahata
    • Journal Title

      Life Sci. 80

      Pages: 1115-1122

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Sodium valproate at therapeutic concentrations changes Ca^<2+> response accompanied with its weak inhibition of protein kinase C in human astrocytoma cells2007

    • Author(s)
      Masatake Kurita, Satoshi Nishino, Kouji Ohtomo, Mayumi Rai, Hisayoshi Shirakawa, Hirobumi Mashiko, Shin-Ichi Niwa, Norimichi Nakahata
    • Journal Title

      Prog. Neuropsychopharmacol. Biol. Psychiat. 31

      Pages: 600-604

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Complanadines C and D, new dimeric alkaloids from Lycopodium complanatum2007

    • Author(s)
      Kan'ichiro Ishiuchl, Takaaki Kubota, Yuzuru Mikami, Yutaro Obara, Norimichi Nakahata, Jun'ichi Kobayashi
    • Journal Title

      Bioorg. Med. Chem. 15

      Pages: 413-417

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel cyathane diterpene, cyrneine A, induces neurite outgrowth in a Racl-dependent mechanism in PC12 cells2007

    • Author(s)
      Yutaro Obara, Tomohiro Hoshino, Maria Carla Marcotullio, Rita Pagiotti, Norimichi Nakahata
    • Journal Title

      Life Sci. 80

      Pages: 1669-1677

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cyathane diterpenes from Sarcodon cyrneus and evaluation of their neuritogenesis and nerve growth factor production2007

    • Author(s)
      Maria Carla Marcotullio, Rita Pagiotti, Federica Maltese, Gildas Norbert Oball-Mond Mwankie, Tomohiro Hoshino, Yutaro Obara, Norimichi Nakahata
    • Journal Title

      Bioorg. Med. Chem. 15

      Pages: 2878-2882

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gタンパク質共役型受容体の新たな機能および調節機構2007

    • Author(s)
      中畑 則道
    • Journal Title

      薬学雑誌 127

      Pages: 1-2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gタンパク質共役型受容体に会合するタンパク質による機能調節2007

    • Author(s)
      中畑 則道, 斎藤 将樹
    • Journal Title

      薬学雑誌 127

      Pages: 3-14

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adenosine A_<2A> receptor-mediated protective effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on retinal ischemia/reperfusion damage in rats2006

    • Author(s)
      Takashi Konno, Ayumi Sato, Takehiro Uchibori, Akihiko Nagai, Kentaro Kogi, Norimichi Nakahata
    • Journal Title

      Brit. J. Ophthalmol. 90

      Pages: 900-905

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Physiological significance of thromboxane A_2 receptor dimerization2006

    • Author(s)
      Masako Sasaki, Katsutoshi Miyosawa, Satoko Ohkubo, Norimichi Nakahata
    • Journal Title

      J. Pharmacol. Sci. 100

      Pages: 263-270

    • NAID

      10018239855

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ATP stimulates interleukin-6 production via P2Y_2 receptor in human HaCaT keratinocytes2006

    • Author(s)
      Hirohide Yoshida, Daisaku Kobayashi, Satoko Ohkubo, Norimichi Nakahata
    • Journal Title

      Eur. J. Pharmacol. 540

      Pages: 1-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Thromboxane A_2 receptor-mediated G_<12/13>-dependent glial morphological change2006

    • Author(s)
      Shigeyoshi Honma, Manami Saika, Satoko Ohkubo, Hitoshi Kurose, Norimichi Nakahata
    • Journal Title

      Eur. J. Pharmacol. 545

      Pages: 100-108

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contribution of extracellular signal-regulated kinase to UTP-induced IL-6 biosynthesis in HaCaT keratinocytes2006

    • Author(s)
      Daisaku Kobayashi, Satoko Ohkubo, Norimichi Nakahata
    • Journal Title

      J. Pharmacol. Sci. 102

      Pages: 368-376

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages2006

    • Author(s)
      Syu-ichi Kanno, Ai Shouji, Ayako Tomizawa, Takako Hiura, Yuu Osanai, Mayuko Ujibe, Yutaro Obara, Norimichi Nakahata, Masaaki Ishikawa
    • Journal Title

      Life Sci. 78

      Pages: 673-681

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Different pathways for activation of extracellular signal-regulated kinase through thromboxane A_2 receptor isoforms2006

    • Author(s)
      Katsuyoshi Miyosawa, Masako Sasaki, Satoko Ohkubo, Norimichi Nakahata
    • Journal Title

      Biol. Pharm. Bull. 29

      Pages: 719-724

    • NAID

      110005602174

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neurotrophic factor secretion from human astrocytoma cells by 2,5,6-tribromogramine via activation of epsilon isoform of protein kinase C2006

    • Author(s)
      Masaki Saito, Megumi Hori, Yutaro Obara, Yasushi Ohizumi, Satoko Ohkubo, Norimichi Nakahata
    • Journal Title

      Eur. J. Pharm. Pharmacol. 28

      Pages: 263-271

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Participation of epoxygenase activation in Saikogenin D-induced inhibition of prostaglandin E_2 synthesis2006

    • Author(s)
      Yasufumi Toriniwa, Lu Xiaochuan, Yasuo Kodama, Yasushi Ohizumi, Makoto Yoshida, Norimichi Nakahata
    • Journal Title

      J. Pharm. Pharmacol. 58

      Pages: 859-866

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neurite outgrowth activity of cyathane diterpenes from Sarcodon cyrneus, Cyrneines A and B2006

    • Author(s)
      Maria Carla Marcotullio, Rita Pagiotti, Federica Maltese, Yutaro Obara, Tomohiro Hoshino, Norimichi Nakahata, Massimo Curini
    • Journal Title

      Planta Medica 72

      Pages: 819-823

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lycopladines B-D and lyconadin B, new alkaloids from Lycopodium complanatum2006

    • Author(s)
      Kan'ichiro Ishiuchi, Takaaki Kubota, Tomohiro Hoshino, Yutaro Obara, Norimichi Nakahata, Jun'ichi Kobayashi
    • Journal Title

      Bioorg. Med. Chem. 14

      Pages: 5995-6000

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitric oxide modulates biphasic contractile response of guinea-pig vas deferens to electrical field stimulation2006

    • Author(s)
      Hironori Nakanishi, Isao Matsuoka, Norimichi Nakahata
    • Journal Title

      Fukushima J. Med. Sci. 52

      Pages: 45-57

    • NAID

      10026159809

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of fluvoxamine on behavioral and psychological symptoms of dementia in alzheimer's disease : a report of three cases2006

    • Author(s)
      Masatake Kurita, Tadahiro Sato, Satoshi Nishino, Koji Ohtomo, Hisayoshi Shirakawa, Hirobumi Mashiko, Shin-ichi Niwa, Norimichi Nakahata
    • Journal Title

      Fukushima J. Med. Sci. 52

      Pages: 143-148

    • NAID

      10026160055

    • Related Report
      2006 Annual Research Report
  • [Presentation] トロンボキサンA_2受容体を介するEGF受容体のトランスアクチベーション機構の解明2008

    • Author(s)
      内山琴美、佐々木雅子、斎藤将樹、小原祐太郎、東山繁樹、中畑則道
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2018-03-28  

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