| Project/Area Number | 09044348 |
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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 Field |
Cell biology
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| Research Institution | Kurume University |
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Principal Investigator |
MEKADA Eisuke 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 Kurume University, PROFESSOR, チルドレンズホスピタル, 教授
SEKIGUCHI Kiyotoshi Kurume University, PROFESSOR, 所長 (50187845)
UMATA Toshiyuki Kurume University, ASSISTANT PROFESSOR, 分子生命科学研究所, 助手 (30213482)
IWAMOTO Ryo Kurume University, ASSISTANT PROFESSOR, 分子生命科学研究所, 助手 (10213323)
TSUNEOKA Makoto Kurume University, ASSISTANT PROFESSOR, 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 |
¥6,900,000 (Direct Cost : ¥6,900,000)
Fiscal Year 1998 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1997 : ¥3,600,000 (Direct Cost : ¥3,600,000)
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| Keywords | HB-EGF / CD9 / Integrin / Cell adhesion / Growth Factors / アポトーシス / ジャクスタクライン |
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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 also known to be a diphtheria toxin receptor. Therefore this protein is a kind of membrane-anchored growth factors in one hand, the specific receptor of the bacteria toxin in the other hand. Dr. Klagsbrun identified HIB-EGF in the cell culture medium and studied biological activities of the soluble form of HB-EGF, while Mekada have studied proHB-EGF as the diphtheria toxin receptor. The aim of this joint meeting is to examine the physiological roles of proHB-EGF in cell growth and developmental processes.
ProHB-EGP 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 integrincalpha3beta1. Studies by immunofluorescence staining showed that the complex cornprised of proHB-EGF, CD9 and integrina#3beta1 co-localizes at cell-cell contact sites, suggesting that
… More
the proHB-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. Less
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