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Mesoderm and neuron induction and activin signaling

Research Project

Project/Area Number 09044316
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Structural biochemistry
Research InstitutionUniversity of Tokushima

Principal Investigator

SUGINO Hiromu  University of Tokushima, The Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)

Co-Investigator(Kenkyū-buntansha) EIJNDENーVAN ふぁん  オランダ国立発生生物学研究所, 上級研究員
SHOJI Hiroki  Kagawa Medical University, Research Associate, 助手 (10263873)
NAKAMURA Takanori  Kagawa Medicla University, Professor, 教授 (70183887)
EIJNDEN-VAN RAAIJ A.J.M.  Netherlands Institute for Developmental Biology, Staff Scientist
RAAIJ A.J.M.  オランダ国立発生生物学研究所, 上級研究員
Project Period (FY) 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsactivin / follistatin / heparan sulfate / apoptosis / development / organizer / endocytosis / オ-ガナイザー / ヘパラン硫酸
Research Abstract

Activin belonging to the TGF-beta superfamily binds to and signals through a receptor complex comprising two transmembrane serine/threonine kinases, called type I and type II.So far, two type II (ActR-IIA,-IIB) and two type I (ActRA-IA,IB) activin receptors have been cloned from mammalian sources. In this study, we attempted to elucidate the role of type I receptors in activin signaling for growth, differentiation and apoptosis, and obtained following results.
(1) We established stable HS-72 transfectants overexpressing ActR-IA or ActR-IB by the electroporation procedure. Overexpression of ActR-IA suppressed activin-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that overexpressed ActR-IB significantly facilitated activin induced apoptosis. These results indicate that ActRA-IA and ActR-IB are distinct from each other … More in activin signal transduction.
(2) Follistain (activin-binding protein) was found to promote the binding of activin to cell surface heparan sulfate. When the cells were incubated with ^<125>I-activin in the presence of follistatin, significant degradation of activin was observed.This activin degradation was abolished by heparan sulfate, chloroquine, and lysosomal protease inhibitors. These results indicate that cell-associated follistain accelerates the uptake of activin into cells, leading to increased degradation by lysosomal enzymes, and thus plays a role in the activin clearance system.
(3) In order to understand the role of follistain-related protein (FRP) in Xenopus embryogenesis, we carried out whole mount in situ hybridization. FRP expression was found to start at stage 10 of Xenopus embryos in the organizer region, suggesting that like follistatin, FRP functions as a organizer factor. The FRP expression in the notochord and floor plate was observed at the neural stage through the tailbud stage, suggesting its role in induction of neural structures. Less

Report

(2 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Jun'ichi Mashimo: "Decrease in the expression of a novel TGF β1-inducible and ras-recision gene,TSC-36,in human cancer cells" Cancer Letters.113. 213-219 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Norio Haneji: "Identification of α-fodrin as a candidate autoantigen in primary Sjogren's syndrome" Science. 276. 604-607 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Osamu Hashimoto: "A novel role of follistatin,an activin-binding protein,in the inhibition of activin action in rat pituitary cells" J.Biol.Chem.272. 13835-13842 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sugino: "Follistatin and its role as an activin-binding protein" The Journal of Medical Investigation. 44. 1-14 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jun'ichi Mashimo: "Decrease in the expression of a novel TGF beta1-inducible and ras-recision gene, TSC-36, in human cancer cells" Cancer Letters.113. 213-219 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Norio Haneji: "Identification of alpha-fodrin as a candidate autoantaigen in primary Sjogren's syndrome" Science. 276. 604-607 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Osamu Hashimoto: "A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells" J.Biol.Chem.272. 13835-13842 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiromu Sugino: "Follistatin and its role as an activin-bindingprotein" The Journal of Medical Investigation.44. 1-14 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jun'ichi Mashimo: "Decrease in the expression of a novel TGF β1-inducible and ras-recision gene,TSC-36,in human cancer cells" Cancer Letters.113. 213-219 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Norio Haneji: "Identification of α-fodrin as a candidate autoantigen in primary Sjogren's syndrome" Science. 276. 604-607 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Osamu Hashimoto: "A novel role of follistatin,an activin-binding protein,in the inhibition of activin action in rat pituitary cells" J.Biol.Chem.272. 13835-13842 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiromu Sugino: "Follistatin and its role as an activin-binding protein" The Jounal of Medical Investigation. 44. 1-14 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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