| Project/Area Number |
20570143
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NOHNO Tsutomu 川崎医科大学, 医学部, 教授 (20098619)
SAGA Yumiko 国立遺伝学研究所, 系統生物研究センター, 教授 (50221271)
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| Co-Investigator(Renkei-kenkyūsha) |
HINO Jun 国立循環器病センター(研究所), 生化学部, 室長 (40260351)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 形態形成 / 発生・分化制御 / 酵素の調節 / 胚葉形成・原腸形成・体節形成 / 発生遺伝 / 進化発生 / 酵素作用の機作 |
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| Research Abstract |
PC6 is a member of the Furin protease family and cleaves prepro-hormones and growth factors into mature proteins. Here we show that PC6 cleaves preproBMP-3b and that it is involved in the axial patterning of vertebrate embryos. Xenopus BMP-3b is expressed in the posterior neural and prechordal plates. However, injected BMP-3b induces anterior markers, and leads to secondary head formation. Since the anteriorizing activity is due to incomplete processing of the BMP-3b precursor, we anticipated that Xenopus BMP-3b protein is cleaved in the posterior neural plate. To address this notion, we examined a protease that can cleave the BMP-3b precursor, and which is expressed in the posterior-neural plate. Like many peptide hormones and growth factors, the BMP-3b-processing enzyme appeared to be tolloid-related or a furin. When injected in combination with BMP-3b, PC6 suppressed secondary head formation triggered by BMP-3b. Western blotting showed that PC6 effectively cleaved the BMP-3b precursor. An inactive PC6 that converted the amino acid of the active center into Phe from Ser, lost these activities. We also confirmed that Xenopus PC6 expression is similar to xBMP-3b, and graded from posterior to anterior. At present, we have been investigating whether the reaction of PC6 and BMP-3b is also conserved in mouse embryos. Our results suggest that the biosynthesis of BMP proteins is related to posterior-ventral patterning and tail formation, whereas abolishing BMP signaling is key to anterior-dorsal patterning and head formation.
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