| Project/Area Number |
03454064
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用生物化学・栄養化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAKI Ryuzo Kyoto University, Agriculture, Professor, 農学部, 教授 (60077378)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1992: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Erythropoietin / Sugar chains / Erythropoiesis / Secretion / Erythropoietin receptor / Polarized secretion / 極性分泌 / 組換え型蛋白質 / 糖鎖の機能 / 糖タンパク質 / 細胞分化増殖因子 |
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| 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.
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