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1992 Fiscal Year Final Research Report Summary

Glycobiology of erythropoietin

Research Project

Project/Area Number 03454064
Research Category

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

Allocation TypeSingle-year Grants
Research Field 応用生物化学・栄養化学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SASAKI Ryuzo  Kyoto University, Agriculture, Professor, 農学部, 教授 (60077378)

Project Period (FY) 1991 – 1992
KeywordsErythropoietin / Sugar chains / Erythropoiesis / Secretion / Erythropoietin receptor / Polarized secretion
Research Abstract

Erythropoietin (EPO) is a physiological stimulator in erythropoiesis. EPO is a heavily glycosylated protein with a molecular mass of 35-39 kDa; half of its molecular weight is sugars. It has three N-linked oligosaccharide chains at amino acid positions 24, 38, and 83 and one O-linked oligosaccaride chain at position 126. This protein is synthesized in adult kidneys and secreted into the circulation to reach hemopoietic tissues. The following biological functions can be assigned to carbohydrates attached to proteins such as EPO that act in the endocrine system. First, the carbohydrates of glycoproteins are needed for their biosynthesis and secretion. Second, carbohydrates confer stability to the protein so that is not eliminated from the circulation during its travel from the production site to its target cells. Third, carbohydrates are involved in the expression by the glycoprotein of its biological function. To elucidate biological functions of sugar chains, the site-directed removal of N-linked sugars of recombinant EPO, and their effects on biosynthesis and biological properties of EPO were investigated. The results indicate that (1) the sugars affect binding affinity to the ligand but do not play a key role in expression of the in vitro activity, (2) they are essential for the expression of the in vivo activity, and (3) N-linked sugars are important for biosynthesis and/or polarized secretion.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yamaguchi,K.: "Effects of site-directed removal of N-glycosylation sites in human erythropoietin on its production and biological properties." J.Biol.Chem.266. 20434-20439 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐々木 隆造: "エリトロポエチンの糖鎖の機能" 生化学. 64. 96-100 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 上田 正次: "医療用タンパク質の糖鎖の構造と機能" 細胞工学. 別冊7. 73-76 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagao,M.: "Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptor." Biochem.Biophys.Res.Commun.188. 888-897 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi, K.: "Effects of site-directed removal of N-glycosylation sites in human erythropoietin on its production and biological properties." J. Biol. Chem.266. 20434-20439 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sasaki, R.: "Functions of sugar chains in erythropoietin." Seikagaku (in Japanese). 64. 96-100 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda, M.: "Structures and functions of sugar chains in medicinal proteins." Cell Technology (in Japanese). 87. 73-76 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagao, M.: "Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptor." Biochem. Biophys. Res. Commun.188. 888-897 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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