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Regulation Mechanisms for Activin Signaling

Research Project

Project/Area Number 13480210
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokushima

Principal Investigator

SUGINO Hiromu  The University of Tokushima, Inst. For Enz. Res., Professor, 分子酵素学研究センター, 教授 (50211305)

Co-Investigator(Kenkyū-buntansha) TSUCHIDA Kunihiro  The University of Tokushima, Inst for Euz. Res., Associate Professor, 分子酵素学研究センター, 助教授 (30281091)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2001: ¥9,300,000 (Direct Cost: ¥9,300,000)
Keywordsactivin / follistatin / FLRG / PDZ / Dok1 / Ser / Thr kinase / Smad / GDF8 / アクチビン受容体 / PDZドメイン / エンドサイトーシス / アポトーシス / Dok-1 / クロストーク
Research Abstract

In this study, we attempted to elucidate molecular mechanisms for activin signal transduction which is regulated either intracellularly or extracellularly by novel protein factors, ARIP (Activin receptor interacting protein) and FLRG (Follistatin lile related gene).
(1) ARIP2 has one PDZ domain in the NH_2-terminal region and one leucine-zipper-like domain in the COOH-terminal region. ARIP2 interacts specifically with activin type II receptors (ActRII) among the receptors for the TGF-β family by the PDZ domain. The COOH-terminal region of ARIP2 interacts with RalBP1. Interestingly, ARIP2 regulates endocytosis of ActRII through the Ral/RalBP1-dependent pathway.
(2) We identified the rasGAP-binding protein (Dok-1) as one of essential proteins responsible for activin-induced apoptosis in mouse B cell. Dok- 1 acts as an adaptor protein linking receptor serine/threonine kinases with the Smads in activin signaling.
(3) ALK7 is an orphan receptor serine/threonine kinase expressed in neuronal tissues as well as in pancreatic islets and pituitary gland. The receptor combination of ActRII and ALK7 is activated more preferentially by activins B and AB rather than Activin A. Activin B responsiveness is largely ALK7-dependent both in neuronal cells and pancreatic β cells.
(4) We identified a mouse follistatin-like protein, FLRG, which has binding activity for the members of TGF-β family such as activin, BMP, myostatin (GDF8) and GDF11. The binding of FLRG to growth factors results in inhibition of their physiolosical functions.

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Tsuchida, K. et al.: "Intracellular and extracellular control of activin function by novel regulatory molecules"Mol.Cell.Endocrinol.. 180. 25-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murase, Y. et al.: "Possible involvement of protein kinases and Smad2 signaling pathways on osteoclast differentiation enhanced by activin A"J.Cell.Physiol.. 188(2). 236-242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatani, M. et al.: "Genomic organization and promoter analysis of mouse follistatin-related gene (FLRG)"Mol.Cell.Endocrinol.. 189(1-2). 117-123 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamakawa, N., et al.: "The rasGAP-binding protein, Dak-1, mediates activin signaling via serine/threonine kinase receptors"EMBO J.. 21(7). 1684-1694 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaki, T., et al.: "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway"J.Biol.Chem.. 277(21). 19008-19018 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto, O., et al.: "cDNA cloning and expression of human activin βE subunit"Mol.Cell.Endocrinol.. 194(1-2). 119-124 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai, K.Y., et al.: "Characterization of rat follistatin-related gene (FLRG) : effects of estrous cycle stage and pregnancy on its mRNA expression in rat reproductive tissues"Biol.Reprod.. 68(1). 199-206 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 土田 邦博 他: "PDZドメインによる機能分子の局在制御と情報クロストーク"実験医学増刊. 20(2). 94-100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuchida, K., et al.: "Intracellular and extracellular control of activin function by novel regulatory molecules."Mol. Cell. Endocrinol.. 180. 25-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murase, Y., et al.: "Possible involvement of protein kinases and Smad2 signaling pathways on osteoclast differentiation enhanced by activin A."J. Cell. Physiol.. 188(2). 236-242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatani, M., et al.: "Genomic organization and promoter analysis of mouse follistatin-related gene (FLRG)."Mol. Cell. Endocrinol.. 189(1-2). 117-123 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamakawa, N., et al.: "The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors."EMBO J.. 21(7). 1684-1694 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaki, T., et al.: "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway."J. Biol. Chem.. 277(21). 19008-19018 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto, O., et al.: "cDNA cloning and expression of human activin βE subunit."Mol. Cell. Endocrinol.. 194(1-2). 119-124 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai, K. Y., et al.: "Characterization of rat follistatin-related gene (FLRG) : effects of estrous cycle stage and pregnancy on its mRNA expression in rat reproductive tissues."Biol. Reprod.. 68(1). 199-206 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatani, M.et al.: "Genomic organization and promoter analysis of mouse follistatin-related gene (FLRG)"Mol. Cell. Endocrinol.. 189(1-2). 117-123 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamakawa, N., et al.: "The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors"EMBO J.. 21(7). 1684-1694 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuzaki, T., et al.: "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway"J. Biol. Chem.. 277(21). 19008-19018 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto, O., et al.: "cDNA cloning and expression of human activin βE subunit"Mol. Cell. Endocrinol.. 194(1-2). 119-124 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arai, K.Y., et al.: "Characterization of rat follistatin-related gene (FLRG) : effects of estrous cycle stage and pregnancy on its mRNA expression in rat reproductive tissues"Biol. Reprod.. 68(1). 199-206 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 土田 邦博 他: "PDZドメインによる機能分子の局在制御と情報クロストーク"実験医学増刊. 20(2). 94-100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchida, K. et al.: "Intracellular and Extracellular Control of Activin Function by Novel Regulatory Molecules"Mol. Cell. Endocrinol.. 180. 25-31 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Murase, Y. et al.: "Possible Involvement of Protein Kinase and Smad2 Signaling Pathways on Osteoclast Differentiation Enhanced by Activin A"J. Cell. Physiol.. 180. 236-242 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamakawa, N. et al.: "The rasGAP-bindig protein, Dok-1, mediates activin signaling via serine/thereonine kinase receptors"EMBO Journal. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakatani, M. et al.: "Genomic organization and promoter analysis of mouse follistatinrelatedgene(FLRG)"Mol. Cell. Endocrinol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 土田邦博 ほか: "PDZドメインによる機能分子の局在制御と情報クロストーク"実験医学増刊. 20(2). 94-100 (2002)

    • Related Report
      2001 Annual Research Report

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

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