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Analyses of the functions of MYPT family, novel anchoring proteins, in cardiovascular system by their knockout and transgenic mice

Research Project

Project/Area Number 12470152
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionMie University

Principal Investigator

NAKANO Takeshi  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60111879)

Co-Investigator(Kenkyū-buntansha) SUZUKI Noboru  Mie University, Life Science Research Center, Associate Professor, 生命科学研究支援センター, 助教授 (00202135)
ITO Masaaki  Mie University, Hospital, Assistant Professor, 医学部附属病院, 講師 (00223181)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywordsmyosin phosphatase / MYPT1 / MYPT2 / knockout mouse / transgenic mouse / phosphorylation of cardiac myosin / Rhoキナーゼ / Proキナーゼ
Research Abstract

MYPT is a target subunit of myosin phosphates (MP), in which MYPT interacts with a catalytic subunit (PP 1 cδ) and the other regulatory subunit, M20. MYPT could also interact with other molecules including RhoA and cGMP-dependent protein kinase Iα, indicating that MYPT has a role as an anchoring protein. MYPT1 is a target subunit of smooth muscle/nonmuscle MP and MYPT2 is that of cardiac/skeletal muscle MP. To investigate the in vivo function of MYPTs, we generated MYPT1-deficient mice and MYPT2 transgenic mice, and analyzed these phenotypes
The heterozygous of MYPT1-deficient mice showed no changes in the expression levels of MYPT1 and no phenotypes as compared with those in the wild type mice, however, none of the F2 mice was homozygous for the MYPT1 deletion, indicating that the targeted disruption of the MYPT1 gene results in embryonic lethality. The point of embryonic lethality is considered to be before 7.5 dpc. These findings indicate that MYPT1 is essential for mouse embryogenes … More is
The transgenic mice overexpressing MYPT2 (Tg) using α-MHC promoter demonstrated a significantly increased expression of MYPT2 (>20 folds) specifically in hearts with a concomitant increase of the endogenous PP1cδ. The phosphorylation levels of regulatory myosin light chain (RLC) in Tg were significantly lower than those in the wild type mice (Wt). These results suggest the specific in vivo interaction of MYPT2 with PP1cδ, which could dephosphorylate RLC in heart. Survival rate, body weight, heart rate and blood pressure were not significantly different between Tg and Wt. Heart weight/body weight ratio of Tg was significantly higher than that of Wt. Echocardiography demonstrated the dilation of LU dimension (LVDd and LVDs) and the moderate impairment of LV function in Tg. These results suggest that the overexpression of MYPT2 and the concomitant increased MP activity decreased LV contractility, resulting in mild LV dilatation. Taken together, MP seems to play a role in cardiac function in vivo Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Mutsumi Koyama: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase"FEBS Letters. 475. 197-200 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tetsuya Hamaguchi: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of myosin phosphatase, by protein kinase N."Biochem.Biophys.Res.Commun.. 274. 825-830 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Haruki Shirato: "Identification and characterization of a novel protein inhibitor of type 1 protein phosphatase"Biochemistry. 39. 13848-13855 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigemasa Araki: "Arachidonic acid-induced Ca^<2+> sensitization of smooth muscle contraction through activation of Rho-kinase"Pflugers Arch.Eur.J.Physiol.. 441. 596-603 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirofumi Machida: "Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene"Biochim.Biophys.Acta. 1517. 424-429 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouji Yamawaki: "Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase"Biochem.Biophys.Res.Commun.. 285. 1040-1045 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumiaki Nakao: "Involvement of Src family protein tyrosine kinases in Ca^<2+>-sensitization of coronary artery contraction mediated by a sphingosylphosphorylcholine-Rho-kinase pathway"Circ.Res.. 91. 953-960 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takafumi Koji: "Addition of angiotensin II receptor antagonist to ACE inhibitor in heart failure improves cardiovascular function by a bradykinin-mediated mechanism"J.Cardiovasc.Pharmacol.. 41. 632-639 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tetsuya Seko: "Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle"Circ.Res.. 92. 411-418 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaaki Ito: "Myosin phosphatase : structure, regulation and function"Mol.Cell.Biochem.. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Moriki: "PhoA activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats"Hyperten.Res.. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mutsumi Koyama, Masaaki Ito, Jianhua Feng, Testuya Seko, Kastuya Shiraki, Koujiro Takase, David J.Hartshorne, Takeshi Nakano: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase"FEBS Lett.. 475. 197-200 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tetsuya Hamagichi, Masaaki Ito, Jianhua Feng, Tetsuya Seko, Mutsumi Koyama, Hirofumi, Machida, Koujiro Takase, Mustumi Amano, Kozo Kaibuchi, David J.Hartshorne, Takeshi Nakano: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of myosin phosphatase, by protein kinase N"Biochem.Biophys.Res.Commun.. 274. 825-830 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harold Shirato, Hiroshi Shima, Gyosuke Sakashita, Takeshi Nakano, Masaaki Ito, Ernest Y C.Lee, Kunimi Kikuchi: "Identification and characterization of a novel protein inhibitor of type-1 protein phosphatase"Biochemistry. 39. 13848-13855 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigemasa Araki, Masaaki Ito, Yasuko Kureishi, Jianfua Feng, Nakoki Isaka, Mutsuki Amano, Kozo Kaibuchi, David J.Hartshorne, Takshi Nakano: "Arachidonic acid-induced Ca^<2+> sensitization of smooth muscle contraction through activation of Rho-kinase"Pflugers Archiv.Eur.J.Physiol.. 441. 596-603 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirofumi Machida, Masaaki Ito, Ryuji Okamoto, Naoki Isaka, David J.Hartshorne, Takeshi Nakano: "Molecular cloning and analysis of 5'-flanking region of human MYPT1 gene"Biochim.Biophys.Acta. 1517(3). 424-429 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouji Yamawaki, Masaaki Ito, Hirofumi Machida, Nobuyuki Moriki, Ryuji Okamoto, Naoki Isaka, Hideto Shimpo, Atsushi Kohda, Katsuzumi Okumura, David J.Hartshorne, Takeshi Nakano: "Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase"Biochem.Biophys.Res.Commun.. 285. 1040-1045 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumiaki Nakao, Sei Kobayashi, Kimiko Mogami, Yoichi Mizukami, Satoshi Shirao, Saori Miwa, Natsuko Todoroki-Ikeda, Masaaki Ito, Masunori Matsuzaki: "Involvement of Src family protein tyrosine kinases in Ca^<2+>-sensitization of coronary artery contraction mediated by a sphingosyl-phosphorylcholine-Rho-kinase pathway"Circ.Res.. 91. 953-960 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takafumi Koji, Katsuya Onishi, Kaoru Dohi, Ryuji Okamoto, Masaki Tanabe, Testuya Kitamura, Masaaki Ito, Naoki Isaka, Tsutomu Nobori, Takeshi Nakano: "Addition of angiotensin II receptor antagonist to ACE inhibitor in heart failure improves cardiovascular function by a bradykinin-mediated mechanism"J.Cardiovasc.Pharmacol.. 41. 632-639 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tetsuya Seko, Masaaki Ito, Yasuko Kureishi, Ryuji Okamoto, Nobuyuki Moriki, Katsuya Onishi, Naoki Isaka, David J.Hartshorne, Takeshi Nakano: "Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle"Circ.Res.. 92. 411-418 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaaki Ito, Takeshi Nakano, Ferenc Erdodi, David J.Hartshorne: "Myosin phosphatase : structure, regulation and function"Mol.Cell.Biochem.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobuyuki Moriki, Masaaki Ito, Tetsuya Seko, Yasuko Kureishi, Ryuji Okamoro, Tetsuya Nakakuki, Mariko Kongo, Naoki Isaka, Kozo Kaibuchi, Takeshi Nakano: "RhoA Activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats"Hyperten.Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumiaki Nakano: "Involvement of Src Family Proien Tyrosine Kinases in Ca^<2+>-Sensitization of Coronary Artery Contraction Mediated by a Sphingosylphosphorylcholine-Rho-kinase Pathway"Circulation Research. 91. 953-960 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Testuya Seko: "Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular Smooth muscle"Circulation Research. 92. 411-418 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takafumi Koji: "Addition of angiotensin II receptor antagonist to ACE inhibitor in heart failure improves Cardiovascular function by a bradykinin-mediaied mechanism"Journal of Cardiovascular Pharmacology. 41・4. 632-639 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirofumi Machida: "Molecular cloning and analysis of 5:flanking region of human MYPT1 gene"Biochim.Biophys.Acta.. 1517. 424-429 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kouji Yamawaki: "Identification of human CPI-17,an inhibitory phosphoprotein for myosin pnospnatase"Biochem.Biophys.Res.Commun.. 285. 1040-1045 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mutsumi Koyama: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase."FEBS Lett.. 475. 197-200 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tetsuya Hamaguchi: "Phosphorylation of CPI-17, an inhibitory phosphoprotein of myosin phosphatase, by protein kinase N."Biochem.Biophys.Res.Commun.. 274. 825-830 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Haruki Shirato: "Identification and characterization of a novel protein inhibitor of type-1 protein phosphatase"Biochemistry. 39. 13848-13855 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigemasa Araki: "Arachidonic acid-induced Ca^<2+> sensitization of smooth muscle contraction through activation of Rho-kinase"Pflugers Archiv.Eur.J.Physiol.. 441. 596-603 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirofumi Machida: "Molecular cloning and analysis of s : flanking region of human MYPT1 gene."Biochim.Biophys.Acta.. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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