| Project/Area Number |
09480198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Kurume University |
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Principal Investigator |
MEKADA Eisuke INSTITUTION,DEPARTMENT,TITLE OF POSITION PROFESSOR, 分子生命科学研究所, 教授 (20135742)
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| Co-Investigator(Kenkyū-buntansha) |
UMATA Toshiyuki INSTITUTION,DEPARTMENT,TITLE OF POSITION ASSISTANT PROF, 分子生命科学研究所, 助手 (30213482)
IWAMOTO Ryo INSTITUTION,DEPARTMENT,TITLE OF POSITION ASSISTANT PROF, 分子生命科学研究所, 助手 (10213323)
TSUNEOKA Makoto INSTITUTION,DEPARTMENT,TITLE OF POSITION ASSISTANT PROF, 分子生命科学研究所, 講師 (50197745)
中村 邦明 久留米大学, 分子生命科学研究所, 日本学術振興会特別研
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | HB-EGF / CD9 / Integrin / Cell adhesion / Growth Factors / アポトーシス / 膜結合型 |
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| Research Abstract |
HB-EGF is a member of EGF family growth factors. The membrane-anchored form of HB-EGF (proHB-EGF) is not only precursor of the soluble form of HB-EGF but also biologically active molecule. ProHIB-EGF forms a complex with other membrane proteins. CD9 and heparan-sulfate proteoglycan(s) associate with proHB-EGF and modulate its biological activities. ProHB-EGF also forms a complex with integrinalpha3beta1. Studies by immunofluorecence staining showed that the complex comprised of proHB-EGF, CD9 and integrinalpha3beta1 co-localizes at cell-cell contact sites, suggesting that the proHIB-EGF complex plays a role in intercellular communication in a juxtacrine manner. In order to know the physiological role of the proHB-EGF complex in a intercellular communication, we have done the following studies and got the results as follows :
1) Upregulation of proHB-EGF activity by CD9
CD9 upregulates the biological activities of proHB-EGF.Regions in both CD9 and proHB-EGF necessary for the upregulation were determined.
2) Growth inhibitory activity of proHB-EGF
We have observed that proHB-EGF shows growth inhibitory activity by juxtacrine mechanism under the culture conditions which soluble forms of HB-EGF and EGF stimulate cell growth. Thus, it is suggested that the soluble form and the membrane-anchored form have different biological activities for cell growth control.
3) Analysis of CD9 null mice
CD9 would have a key role to connect proHB-EGF with integrinalpha3beta1. To analyze the physiological role of proHB-EGF complex CD9 null mice were generated. CD9 null mice were born and seem healthy, but showed severe defect in reproductive system. Further studies are now in progress.
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