1998 Fiscal Year Final Research Report Summary
Juxtacrine Growth Control with HB-EGF Complex
| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | HB-EGF / CD9 / Integrin / Cell adhesion / Growth Factors / アポトーシス |
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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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