| Project/Area Number |
06044214
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kurume University |
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Principal Investigator |
MEKADA Eisuke Institute of Life Science Kurume University, Professor, 分子生命科学研究所, 教授 (20135742)
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| Co-Investigator(Kenkyū-buntansha) |
KLAGSBRUN Michael Harvard Medical School, Children's Hospital Faculty Research Council, チルドレンズホスピタル, 教授
SEKIGUCHI Kiyotoshi Research Institute Osaka Medical Center for Maternal and Child Health, 教授 (50187845)
HIGASHIYAMA Shigeki Department of Biochemistry Osaka University, Professor, 医学部生化学教室, 助手 (60202272)
MITAMURA Toshihide Research Institute for Microbial Diseases Osaka University, Assistant Professor, 微生物病研究所, 助手 (80268846)
UMATA Toshiyuki Institute of Life Science Kurume University, Assistant Professor, 分子生命科学研究所, 助手 (30213482)
IWAMOTO Ryo Institute of Life Science Kurume University, Assistant Professor, 分子生命科学研究所, 助手 (10213323)
TSUNEOKA Makoto Institute of Life Science Kurume University, Assistant Professor, 分子生命科学研究所, 講師 (50197745)
MICHAEL Klag ハーバード大学, チルドレンズホスピタル, 教授
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1996: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1994: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | juxtacrine / integrin / HB-EGF / CD9 / TM4 / haparansulfate proteoglycans / membrane-anchored growth factors / 細胞接着 / ジフテリア毒素リセプター / 細胞増殖因子 |
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| Research Abstract |
We have found that the membrane-anchored form of heparin-binding EGF-like growth factor (proHB-EGF) has a juxtacrine mitogenic activity. ProHB-EGF associates with tetramembrane-spanning protein CD9. CD9 was found to enhance the juxtacrine mitogenic activity of proHB-EGF.Furthermore, proHB-EGF forms a complex with integrin alpha3beta1. The aim of this study is to understand the physiological role of this complex. We have done sevaral experiments and obtained the following results.
(1) Localization of the complex
Vero cell, derived from monkey kidney, was studied by immunofluorescence using specific antibodies to proHB-EGF,CD9, integrin alpha3, and integrin beta1. The results revealed that proHB-EGF,CD9 and integrin alpha3b1 localized at cell-cell junction region.
(2) The role of heparin-binding domain (KBD)
To analyze the role of HBD domain of proHB-EGF,the deletion mutants of HBD of proHB-EGF were produced. The results showed that HBD is not essential for the mitogenic activity and diphtheria toxin binding activity. Heparansulfate proteoglycans may modulate the mitogenic activity of proHB-EGF by interacting with the HBD domain of proHB-EGF.
These results indicate that proHB-EGF may play the role of cell-cell interaction in a large complex.
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