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Roles of activin/follistatin in neural induction

Research Project

Project/Area Number 10044298
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
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) OGURA Yasunori  University of Tokushima, The Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (60304557)
TSUCHIDA Kunihiro  University of Tokushima, The Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (30281091)
EIJINDENーVAN エージェイ  オランダ国立発生生物学研究所, 上級研究員
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsactivin / activin receptor / PDZ domain / WW domain / Smad / synapse / follistatin / 神経細胞 / TSC-36 / 中胚葉
Research Abstract

The aim of this project is to elucidate the roles of activin and follistatin in neural induction in embryogenesis. In this period, we have obtained the following findings.
(1) Identification and characterization of a PDZ protein.
We have identified a mouse PDZ protein that interacts with the activin type IIA receptor (ActRIIA), which we named ARIP1 (activin receptor interacting protein 1 ). By using yeast two-hybrid screening, we isolated a cDNA clone of ARIP1 from a mouse brain cDNA library. ARIPI had one guanylate kinase domain (Guk) in the NH2-terminal region, followed by two WW domains and five PDZ domains (PDZ1-5). ARIP1 interacted with ActRIIA through PDZ5. The COOH-terminal residues of ActRIIA (E-S-S-L) agree with a PDZ-binding consensus motif, and ARIP1 recognized the consensus sequence. ARIP1 interacts specifically with ActRIIA among the receptors for TGF-β family. Interestingly, ARIP1 also interacted with Smad3, which is an activin/TGF-β intracellular signaling molecule. The mR … More NA of ARIP1 was more abundant in the brain that in other tissues. Overexpressin of ARIP1 controls activin-induced and Smad3-induced transcription in activin-responsive cell lines. These findings suggest that ARIP1 has a significant role in assembling activin signaling molecules at specific subcellular sites and in regulating signal transduction in neuronal cells.
(2) Characterization of a novel follistatin-like protein as an activin-binding protein.
We have identified a novel follistatin-like protein in humans and mice, which was found to differ from known follistatin gene products. Follistatin has three follistatin domains that are presumed to be growth factor binding motifs. Both the human and mouse follistatin-like proteins possessed only two follistatin domains. Northen blotting revealed that mRNAs for the novel follistatin-like proteins were abundantly expressed in placenta, adrenal gland, lung, heart, pituitary, testis and ovary, tissues where activins are also abundantly expressed. The recombinant proteins were found to have an activin-bindig activity as revealed by coimmunoprecipitation analysis. Furthermore, the recombinant protein inhibited activin-induced transcriptional responses in activin-responsive cells I n a dose-dependent manner. Ligand blotting using ィイD1125ィエD1I-activin and GST-pull down analysis revealed that the second follistatin domain in the C-terminal region on the molecule was responsible for the activin-binding activity. In summary, we have identified a novel follistatin possessing activin-binding activity. Our finding implies that cellular signaling of activin is tightly regulated by multiple members of the follistatin family. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Okabayashi,K.et al.: "cDNA Cloning and Distribution of the Xenopus Follislatin-Related Protein"Biochem.Biophys.Res.Commun.. 254. 42-48 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishisaki,A.et al.: "Differential Inhibition of Smad6 and Smad7 on Bone Morphogenetic Protein- and Activin-mediated Growth Arrest and Apoptosis in B Cells"J.Biol.Chem.. 274. 13637-13642 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyamoto,S.et al.: "Effects of activin on hormone secretion by signal female tat pituitary cells:analysis by cell immunoblot assay"J.Endccrinol.. 161. 375-382 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji,H.et al.: "Identification and characterization of a PDZ protein that interacts with activin type II receptors"J.Biol.Chem.. 275(8). 5485-5492 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumitomo,K.et al.: "Expression of TGF-β inducible gene,TSC-36,causes growth inhibition in human lung cancer cell lines"Cancer letters. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugino,H.et al.: "Skeletal Growth Factors(Canalis,E.ed)Chapter I Activin aund follistatin"Lippincott Williams & Willkins,Philadelphia.(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okabayashi, K. et al.: "cDNA Cloning and Distribution of the Xenopus Follistatin-Related Protein."Biochem. Biophys. Res. Commun.. 254. 42-48 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishisaki, A. et al.: "Differential Inhibition of Smad6 and Smad7 on Bone Morphogenetic Protein- and Activin-mediated Growth Arrest and Apoptosis in B Cells."J, Biol. Chem.. 274. 13637-13642 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyamoto, S. et al.: "Effects of activin on hormone secretion by signal female rat pituitary cells: analysis by cell immunoblot assay."J. Endocrinol.. 161. 375-382 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shoji, H. et al.: "Identification and characterization of a PDZ protein that interacts with activin type II receptors."J. Biol. Chem.. 275(8). 5485-5492 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumitomo, K. et al.: "Expression of TGF-b inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines."Cancer letters. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugino, H. et al.: "Skeletal Growth Factors (Canalis, E. ed) Chapter I Activin and follistatin"Lippincott Williams & Willkins, Philadelphia.. (in press) (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okabayashi,K.et al.: "cDNA Cloning and Distribution of the Xenopus Follistatin-Related Protein."Biochem.Biophys.Res.Commun.. 254. 42-48 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishisaki,A.et al.: "Differential Inhibition of Smad6 and Smad7 on Bone Morphogenetic Protein-and Activin-mediated Growth Arrest and Apoptosis in B Cells."J.Biol.Chem.. 274. 13637-13642 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamoto,S.et al.: "Effects of activin on hormone secretion by signal female rat pituitary cells: analysis by cell immunoblot assay."J.Endocrinol.. 161. 375-382 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shoji,H.et al.: "Identification and characterization of a PDZ protein that interacts with activin type II receptors."J.Biol.Chem.. 275(8). 5485-5492 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sumitomo,K.et al.: "Expression of TGF-β inducible gene,TSC-36,causes growth inhibition in human lung cancer cell lines."Cancer letters. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sugino,H.et al.: "Skeletal Growth Factors (Canalis,E.ed) Chapter I Activin and follistatin"Lippincott Williams & Willkins,Philadelphia.(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamane,Y.,et al: "Molecular Characterization of Xenopus Embryo Heparan Sulfate:Differential Structural Requirements for the Specific Binding to Basic Fibroblast Growth Factor and Follistatin." J.Biol.Chem.273. 7375-7381 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaoka,T.,et al.: "Hypoplasia of Pancreatic Islets in Transgenic Mice Expressing Activin Receptor Mutants." J.Clin.Invest.102. 294-301 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iemura,S.,et al.: "Direct Binding of Follistatin to a Complex of Bone Morphogenetic Protein and its Receptor Inhibits Ventral and Epidermal Cell Fates in Early Xenopus Embryo." Proc.Natl.Acad.Sci.U.S.A.95. 9337-9342 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoji,H.,et al.: "Identification of a Novel Type II Activin Receptor,Type IIA-N,Induced During the Neural Differentiation of Murine P19 Embryonal Carcinoma Cells." Biochem.Biophys.Res.Commun.246. 320-324 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohguchi,M.,et al.: "Activin A Regulates the Production of Mature Interleukin-1β and Interleukin-1 Receptor Antagonist in Human Monocytic Cells." J.Inter.Cyto.Res.18. 491-498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hashimoto,O.,et al.: "The Role of Activin TypeI Receptors in Activin A-induced Growth Arrest and Apoptosis in Mouse Cell." Cell.Signal.10. 743-749 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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