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Signal Transduction Mechanism in differentiation and Development of Follicular Granulosa Cells.

Research Project

Project/Area Number 02454541
Research Category

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

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

SUGINO Hiromu  The Institute of Physical and Frontier Research System, Researcher Chemical Research, フロンティア研究システム, 研究員 (50211305)

Co-Investigator(Kenkyū-buntansha) 粉川 京子  理化学研究所, フロンティア研究システム, 研究員
NAKAMURA Takanori  The Institute of Physical and Frontier Research System, Researcher Chemical Rese, フロンティア研究システム, 研究員 (70183887)
KOGAWA Kyoko  The Institute of Physical and Frontier Research System, Researcher chemical Rese
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsActivin / Activin-binding protein / Activin receptor / EC cell / Mesoderm induction / Heparan sulfate / Embryo / ホリスタチン / 受容体 / 結合蛋白質 / 分化誘導 / 細胞接着性 / 硫酸多糖 / FSH
Research Abstract

Activin was originally isolated from mammalian ganads as a stimulator for FSH secretion by pituitary cells. the primary structures was found to be very similar to TGF-beta. Recent studies have verified that, like TGF-beta, mfivin has vadous fimctions in various biological reactions including development, differentiation and morphogenesis. In this project, we focused on elucidation of the mechanism for activin signal msduction.
(1)We found in rat ovaly and bovine pituitary an activin-binding protein with a specific and high affinity for activin, and proved that it was identical to follistatin, which was initially obtained from pig ovary as an FSHsecretion suppressor. We also demonstrated that follistatin exerts a neutralizing effect on activin activity in various systems. These inhibitory effects of follistatin on activin actions can be explained by our finding that folhstatin binds directly to activin to form an inactive complex. Follistatin very likely plays a significant role in the regulation of various actions of activin. (2)Follistatin secreted by cultured rat granulosa cells was shown to associate with cell surface by affinity labeling with ^<125>I-activin. It bound to the heparan sulfate side chains of proteoglycans on the cell surface. Cell-bound follistatin may capture activin in the matrix and at the cell surface and regurate the various actions of activin. (3)An activin receptor protein was isolated by affinity chromatography on an activin-immobilizedcolumn from membrane fractions of several cell cultures including mouse Friend leukemia cell F5-5, human erythroleukemia cell K562 and mouse EC cell P19. SDS-PAGE of the prepretion showed one band of 70 kDa. The amino acid sequence of the first 18 residues revealed that the purified receptor is a member of the activin receptor family.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Kyoko Kogawa: "Activin-Binding Protein Is Presents in Pituitary," Endocrinology. 128. 1434-1440 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Asashima: "Follistatin Inhibits the Mesoderm-Inducing Activity of Activin A and the Vegetalizing Factor from Chicken Embryo." Roux's Arch.Dev.Biol.200. 4-7 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taei Matsui: "B-Subunits of Equine Chorionic Gonadotropin and Leuteinizing Hormone with an Identical Amino Acid Sequence Have Different Asparagine-Linked Oligo-Saccharide Chains." Biochem.Biophys.Res.Commun.174. 940-945 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sachiko Saito: "Production of Activin-Binding Protein by Rat Granulosa Cells in uitro." Biochem.Biophys.Res.Commun.176. 413-422 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sachiko Saito: "Characterization of Antisera Directed against Follistatin/Activin-binding Protein Peptides." Endocrinol.Japon.38. 377-382 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kyoko Kogawa: "Immunohistochemical Localization of Follistatin in Rat Tissues" Endocrinol.Japon.38. 383-391 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Hashimoto: "Follistatin Is a Developmentally Regulated Cytokine in Neural Differentiation." J.Biol.Chem.267. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takanori Nakamura: "Isolation and Characterization of Activin B:Evidence for Its Potent Xenopus Mesoderm-Inducing Activity." Science.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tetsuro Katayama: "Paracrine Effect of Folliculo-Stellate Cells on the Growth Factor-Like Actions of Activin A in Anterior Pituitary Cultures." Mol.Cell.Endocrinol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kenji Ogawa: "Immunoreactive Follistatin in Preovulatory Follicles Is Down-Regulated by Primary Gonadotropin Surges in Proestrus Rat" Endocrinology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takanori Nakamura: "Follistatin,an Activin-Binding Protein,Associates with Heparan Sulfate Chains of Proteoglycans on Follicular Granulosa Cells" J.Biol.Chem.266. 19432-19437 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Asashima: "The Presence of Activin (Erythroid Differentiation Factor)in Unfertilized Eggs and Blastulae of Xenopus laevis." Proc.Natl.Acad.Sci.U.S.A.88. 6511-6514 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kishiko Sugino: "Purification and Characterization of High Molecular Weight Forms of Inhibin from Bovine Follicular Fluid." Endocrinology. 130. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Shiozaki: "Evidence for the Participation of Endogenous ActivinA/Erythroid Differentiation Factor in the Regulation of Erythropoiesis." Proc.Natl.Acad.Sci.U.S.A.89. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Asashima: "The Vegetalizing Factor from Chicken Embryos:Its EDF(Activin A)-like Activity." Mechanisms Dev.34. 135-141 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takanori Nakamura: "Follistatin Inhibits Activin-Induced Differentiation of Rat Follicular Granulosa Cells in vitro" Biochem.Biophys.Acta. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kogawa, K.: "Activin-Binding Protein Is Present in Pituitary." Endocrinology. 128. 1434-1440 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Asashima, M.: "The Presence of Activin (Erythroid Differentiation Factor) in Unfertilized Eggs and Blastulae of Xenopus laevis." Proc. Natl. Acad. Sci. U. S. A.88. 6511-6514

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Asashima, M.: "Follistatin Inhibits the Mesoderm-Inducing Activity of Activin A and the Vegetalizing Factor from Chicken Embryo." Roux's Arch. Dev. Biol.200. 4-7 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Saito, S.: "Production of Activin-Binding Protein By Rat Granulosa Cells in Vitro." Biochem. Biophys. Res. Commun.176. 413-422 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Matui, T.: "E*-Subunits of Equine Chorionic Gonadotropin and Luteinizing Hormone with an Identical Amino Acid Sequence Have Different Asparagine-Linked Oligo-Saccharide Chains." Biochem. Biophys. Res. Commun.174. 940-945 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Saito, S.: "Characterization of Antisera Directed against Follistatin/Activin-Binding Protein Peptides." Endocrinol. Jpn.38. 377-382 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kogawa, K.: "Immunohistochemical Localization of Follistatin in Rat Tissues." Endocrinol. Jpn.38. 383-391 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Asashima, M.: "The Vegetalizing Factor from Chicken Embryos : Its EDF (Activin A) -like Activity." Mechanisms Dev.34. 135-141 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakamura, T.: "Follistatin, an Activin- Binding Protein, Associates with Heparan Sulfate Chains of Proteoglycans on Follicular Granulosa Cells." J. Biol. Chem.266. 19432-19437 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shiozaki, M.: "Evidence for the Participation of Endogenous Activin A/Erythroid Differentiation Factor in the Regulation of Erythropoiesis." Proc. Natl. Acad. Sci. U. S. A.89. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugino, K.: "Purification and Characterization of High Molecular Weight Forms of Inhibin from Bovine Follicular Fluid." Endocrinology. 130. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakamura, T.: "Follistatin Inhibits Activin-Induced Differentiation of Rat Follicular Granulosa Cells in virto." Biochem. Biophys. Acta.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto, M.: "Follistatin Is a Developmentally Regulated Cytokine in Neural Differentiation." J. Biol. Chem.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakamura, T.: "Isolation and Characterization of Activin B : Evidence for Its Potent Xenopus Mesoderm-Inducing Activity." Science.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Katayama, T.: "Paracrine Effect of Folliculo-Stellate Cells on the Growth Factor-Like Actions of Activin A in Anterior Pituitary Cultures." Mol. Cell. Endocrinol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ogawa, K.: "Immunoreactive follistatin in Preovulatory Follicles Is Down-Regulated by Primary Gonadotropin Surges in Proestrus Rat." Endocrinology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sachiko Saito: "Characterization of Anti-sera Directed against Follistatin/Activin-finding Protein Peptides." Endocrinol:Japon. 38. 377-382 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kyoko Kogawa: "Immunohisto chemical Localization of Follistatin in Rat Tissues." Endocrinol.Japon. 38. 383-391 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tokanori Nakamura: "Follistation,an Activin-Binding Protein,Associates with Heparan Suefate Chains of Proteoglycans on Follicular Cells." J.Biol.Chem.266. 19432-19437 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kishiko Sugino: "Purification and Characterization of High Molicular weight Forms of Inhifin from Bouine Follicular Fluid." Endocrinology. 130. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Makato Asashima: "The Presence of Activin(Erythroid Differentiation Factor) in Unferfilized Eggs and Blastulae of Xenopus laevis." Proc.Natl.Acad.Sei.U.S.A.88. 6511-6514 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Makoto Shiozaki: "Evidence for the Participation of Endogenous Activin A/Erythroid Differentiation factor in the Regulation of Erythropoiesis" Proc.Natl.Acad.Sci.U.S.A. 89. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Makoto Asashima: "The Vegetalizing Factor from Chicken Embryos:Its EDF(Activin A)-like Activity." Mechanisms Dev.3. 34. 135-141 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takanori Nakamura: "Follistatin Inhibits Activin-Induced Differetiation of Rat Follicular Granulosa Cells in vitro." Biochem.Biophys.Acta. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Makoto Hashimoto: "Follistatin Is a Developmentally Regulated Cytokine in Neural Differentiation" J.Biol.Chem.267. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takanori Nakamura: "Isolation and Characterization of Activin B:Evidence for Its Potent Xenopus Mesoderm -Inducing Activity." Science.

    • Related Report
      1991 Annual Research Report
  • [Publications] Tetsuro Katayama: "Paracrine Effect of Folliculo-Stellate Cells on the Growth Factor-Like Actions of Activin A in Anterior pituitary Cultures" Mol.Cell.Endcrinol.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kenji Ogawa: "Immunoreactive Follistatin in Preovulatory Follicles Is Down-Regulated by Primary Gonadotropin Surges in Proestrus Rat" Endocrinology.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kyoko Kogawa: "ActivinーBinding protein Is Present in Pituitary." Endocrinology. 128. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Makoto Asashima: "Follistatin Inhibits the MesodermーInducing Activity,of Activin A and the Vegetalizing Factor from Chicken Embryo." Roux' Archives Develop.Biol. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Taei Matsui: "βーSubunit of Equine Chorionic Gonadotropin and Luteiniztion Hormone with an Identical Amino Acid Sequence Hove Different AsparagineーLinked Oligosaccharide." Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sachiko saito: "production of ActivinーBinding protein by Rat Granulosa cells in vitro." Biochem.Bioplys.Res Commun.(1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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