Role of G protein-coupled receptor kinase 5 in myocardial infarction

• Project/Area Number: 22590083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyushu University
• Principal Investigator: NAKAYA Michio 九州大学, 薬学研究院, 准教授 (80464387)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心臓 / G蛋白質共役型7回膜貫通型受容体キナーゼ / 心筋梗塞 / Ｇ蛋白質共役型７回膜貫通型受容体キナーゼ

Research Abstract

G protein-coupled receptor kinases (GRKs) were initially identified as molecules that phosphorylate G-protein coupled receptors, leading to their desensitization. We first found that GRK5 expression was significantly increased in the infarct area of left ventricle after myocardial infarction (MI). We next examined the mortality rate of WT and β-arrestin2 KO mice after MI. GRK5 KO mice were more prone to die than WT mice after MI.

Research Products

• [Journal Article] GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance (2013)
  • Author(s): Nakaya M, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, Nishihara H, Ohba M, Komiya S, Tani N, Nishida M, Taniguchi H, Sato Y, Matsumoto M, Tsuda M, Kuroda M, Inoue K, Kurose H
  • Journal Title: Nature Commun Volume: 4 Issue: 1 Pages: 1532-1532
  • DOI: 10.1038/ncomms2540
  • Peer Reviewed
• [Journal Article] Attenuated desensitization of b-adrenergic receptor by water-soluble N-nitrosamines that induce S-nitrosylation without NO release (2013)
  • Author(s): Noriko Makita*, Yoji Kabasawa*, Yuko Otani, Firman, Junichiro Sato, Makiko Hashimoto, Michio Nakaya, Hiroaki Nishihara, Masaomi Nangaku, Hitoshi Kurose, Tomohiko Ohwada, Taroh Iiri
  • Journal Title: Circ. Res Volume: 112 Issue: 2 Pages: 327-334
  • DOI: 10.1161/circresaha.112.277665
  • Peer Reviewed
• [Journal Article] Induction of cardiac fibrosis by b-blocker in G protein-independent but GRK5/b-arrestin2-dependent signaling pathways (2012)
  • Author(s): Michio Nakaya, Satsuki Chikura, Kenji Watari, Natsumi Mizuno, Koji Mochinaga, Supachoke Mangmool, Satoru Koyanagi, Shigehiro Ohdo, Yoji Sato, Tomomi Ide, Motohiro Nishida & Hitoshi Kurose
  • Journal Title: J. Biol. Chem Volume: 287 Issue: 42 Pages: 35669-35677
  • DOI: 10.1074/jbc.m112.357871
  • Peer Reviewed
• [Journal Article] Attenuated desensitization of β-adrenergic receptor by water-soluble N-nitrosamines that induce S-nitrosylation without NO release. (2012)
  • Author(s): Makita N et al.
  • Journal Title: Circ. Res. Volume: 112 Pages: 327-334
  • Peer Reviewed
• [Journal Article] Protein kinase A-mediated phosphorylation of TRPC6 channels underlies suppression of angiotensin II-induced vasoconstriction (2011)
  • Author(s): Nishioka K, Nishida M, Ariyoshi M, Saiki S, Jian Z, Hirano M, Nakaya M, Sato Y, Kita S, Iwamoto T, Hirano K, Inoue R, Kurose H
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. Volume: 31 Issue: 10 Pages: 2278-2286
  • DOI: 10.1161/atvbaha.110.221010
  • Peer Reviewed
• [Journal Article] TRPC3-mediated Ca^<2+> influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts (2011)
  • Author(s): Kitajima N, Watanabe K, Morimoto S, Sato Y, Kiyonaka S, Hoshijima M, Ikeda Y, Nakaya M, Ide T, Mori Y, Kurose H, Nishida M
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 409 Issue: 1 Pages: 108-113
  • DOI: 10.1016/j.bbrc.2011.04.124
  • Peer Reviewed
• [Journal Article] Heterologous down-regulation of angiotensin type1 receptors by purinergic P2Y_2 receptor stimulation through S-nitrosylation of NF-κB (2011)
  • Author(s): Nishida M, Ogushi M, Suda R, Toyotaka M, Saiki S, Kitajima N, Nakaya M, Kim K-M, Ide T, Sato Y, Inoue K, Kurose H
  • Journal Title: Proc.Natl.Acad.Sci.USA. Volume: 108 Issue: 16 Pages: 6662-6627
  • DOI: 10.1073/pnas.1017640108
  • Peer Reviewed
• [Journal Article] Cilostazol suppresses angiotensin II-induced vasoconstriction via prote in kinase A-mediated phosphorylation of the transient receptor potential canonical 6 channel (2011)
  • Author(s): Nishioka K, et al
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. Volume: 31 Pages: 2278-2286
  • Peer Reviewed
• [Journal Article] TRPC3-mediated Ca2+ influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts (2011)
  • Author(s): Kitajima N, et al
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 409 Pages: 108-113
  • Peer Reviewed
• [Journal Article] Heterologous down-regulation of angiotensin type 1 receptors by purinergic P2Y2 receptor stimulation through S-nitrosylation of NF-kappa B (2011)
  • Author(s): Nishida M, et al
  • Journal Title: Proc.Natl.Acad.Sci.USA. Volume: 108 Pages: 6662-6667
  • Peer Reviewed
• [Journal Article] Determining the activation of rho as an index of receptor coupling to G12/13 proteins (2011)
  • Author(s): Nakaya M, et al
  • Journal Title: Methods.Mol.Biol. Volume: 746 Pages: 317-327
• [Journal Article] Regulation of Angiotensin II receptor signaling by cysteine modification of NF-κB (2011)
  • Author(s): Nishida M, et al
  • Journal Title: Nitric Oxide Volume: 25 Pages: 112-117
  • Peer Reviewed
• [Journal Article] Regulation of Angiotensin II receptor signaling by cysteine modification of NF-κB (2011)
  • Author(s): Nishida M, et al.
  • Journal Title: Nitric oxide Volume: (In press)
  • Peer Reviewed
• [Journal Article] Pertussis toxin upregulates angiotensin type 1 receptors through Toll-like receptor 4-mediated Rac activation. (2010)
  • Author(s): Nishida M, et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 15268-15277
  • Peer Reviewed
• [Journal Article] Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition. (2010)
  • Author(s): Nishida M, et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 13244-13253
  • Peer Reviewed
• [Presentation] 心筋梗塞時におけるGRK5の役割解析 (2013)
  • Author(s): 仲矢道雄、黒瀬等
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] 受容体シグナリングにおけるイメージング技術の応用 (2012)
  • Author(s): 仲矢道雄
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(北海道)(招待講演)
  • Year and Date: 2012-03-30
• [Presentation] Gタンパク質共役型受容体キナーゼ/βアレスチンを介した新規機能 (2012)
  • Author(s): 仲矢道雄
  • Organizer: 第85回日本薬理学会
  • Place of Presentation: 京都国際会館(京都)(招待講演)
  • Year and Date: 2012-03-15
• [Presentation] アポトーシス細胞の貪食におけるGRK6の関与 (2012)
  • Author(s): 仲矢道雄、黒瀬等
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 受容体シグナリングにおけるイメージング技術の応用 (2012)
  • Author(s): 仲矢道雄
  • Organizer: 日本薬学会 第132年会
  • Place of Presentation: 札幌
• [Presentation] G タンパク質共役型受容体キナーゼ/βアレスチンを介した新規機能 (2012)
  • Author(s): 仲矢道雄、千蔵さつき、渡健治、西田基宏、黒瀬等
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
• [Presentation] G蛋白質非依存的かつGRK5/βアレスチン2依存的なβアドレナリン受容体遮断薬による心臓の線維化 (2011)
  • Author(s): 仲矢道雄
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-29
• [Presentation] Induction of cardiac fibrosis by β-blocker in G protein-independent but GRK5/β-arrestin2-dependent signaling pathways (2011)
  • Author(s): 仲矢道雄
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-22
• [Presentation] βアドレナリン受容体遮断薬のGRK5/βアレスチン2を介した心臓の線維化 (2011)
  • Author(s): 仲矢道雄、西田基宏、黒瀬等
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] Induction of cardiac fibrosis by ss-blocker in G protein-independent but GRK5/ss-arrestin2-dependent signaling pathways (2011)
  • Author(s): 仲矢道雄、西田基宏、黒瀬等
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] アポトーシス細胞の貪食におけるGRK6の関与
  • Author(s): 仲矢道雄
  • Organizer: 第８５回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Invited
• [Presentation] 心筋梗塞時におけるGRK5の役割解析
  • Author(s): 仲矢道雄
  • Organizer: 日本薬学会 第１３３年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Invited
• [Book] 医学のあゆみ G蛋白質共役受容体研究 (2010)
  • Author(s): 仲矢道雄, ら計3名
  • Publisher: 医歯薬出版株式会社
• [Book] Nippon Yakurigaku Zasshi 135巻5号 (2010)
  • Author(s): 西田基宏, ら計4名
  • Publisher: 日本薬理学会
• [Book] Yakugaku Zasshi 130巻11号 (2010)
  • Author(s): 西田基宏, ら計6名
  • Publisher: 日本薬学会
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  • URL: http://chudoku.phar.kyushu-u.ac.jp/