Juxtacrine Growth Control with HB-EGF Complex

使用 HB-EGF 复合物进行近分泌生长控制

基本信息

批准号：
09480198
负责人：
MEKADA Eisuke
金额：
$ 2.62万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480198/
关键词：
HB-EGF CD9 Integrin Cell adhesion Growth Factors アポトーシス膜結合型

项目摘要

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 CD9CD9 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-EGFWe 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 miceCD9 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.

HB-EGF是EGF家族生长因子的成员。膜锚定形式的 HB-EGF (proHB-EGF) 不仅是可溶形式 HB-EGF 的前体，而且是生物活性分子。 ProHIB-EGF 与其他膜蛋白形成复合物。 CD9 和硫酸乙酰肝素蛋白聚糖与 proHB-EGF 结合并调节其生物活性。 ProHB-EGF 还与整合素α3β1 形成复合物。免疫荧光染色研究表明，由 proHB-EGF、CD9 和 integrinalpha3beta1 组成的复合物共定位于细胞-细胞接触位点，表明 proHIB-EGF 复合物以近分泌方式在细胞间通讯中发挥作用。为了了解proHB-EGF复合物在细胞间通讯中的生理作用，我们做了以下研究并得到如下结果：1)CD9CD9上调proHB-EGF活性上调proHB-EGF的生物活性。确定了 CD9 和 proHB-EGF 中上调所需的区域。 2) proHB-EGF 的生长抑制活性我们观察到 proHB-EGF 通过以下方式显示生长抑制活性：可溶形式的 HB-EGF 和 EGF 刺激细胞生长的培养条件下的近分泌机制。因此，表明可溶形式和膜锚定形式对于细胞生长控制具有不同的生物活性。3)CD9缺失小鼠的分析CD9对于连接proHB-EGF与整合素α3β1具有关键作用。为了分析 proHB-EGF 复合物的生理作用，生成了 CD9 缺失小鼠。 CD9缺失小鼠出生后看起来很健康，但生殖系统表现出严重缺陷。进一步的研究正在进行中。