The role of membrane-anchored HB-EGF on cell growth

膜锚定的HB-EGF对细胞生长的作用

基本信息

批准号：
09044348
负责人：
MEKADA Eisuke
金额：
$ 4.42万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
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-09044348/
关键词：
HB-EGF CD9 Integrin Cell adhesion Growth Factors アポトーシスジャクスタクライン

项目摘要

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

HB-EGF 是 EGF 家族生长因子的成员，HB-EGF (proHB-EGF) 的膜锚定形式也被认为是白喉毒素受体，因此该蛋白是一种膜锚定生长因子。另一方面，Klagsbrun 博士一方面鉴定了细胞培养基中细菌毒素的特异性受体，并研究了可溶形式的 HB-EGF 的生物活性。 Mekada 研究了 proHB-EGF 作为白喉毒素受体，本次联席会议的目的是研究 proHB-EGF 在细胞生长和发育过程中的生理作用。ProHB-EGP 与其他膜蛋白 CD9 和乙酰肝素形成复合物。硫酸盐蛋白聚糖与 proHB-EGF 结合并调节其生物活性，通过免疫荧光染色研究，ProHB-EGF 也与整合素α3β1 形成复合物。研究表明，由 proHB-EGF、CD9 和 integrina#3beta1 组成的复合物共定位于细胞间接触位点，这表明 proHB-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）CD9上调proHB-EGF活性：CD9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 在近分泌机制下显示出生长抑制活性。可溶形式的HB-EGF和EGF刺激细胞生长的培养条件因此，表明可溶形式和膜锚定形式对于细胞生长具有不同的生物活性。 3)CD9缺失小鼠的分析：CD9在连接proHB-EGF与整合素α3β1方面具有关键作用。为了分析proHB-EGF复合物的生理作用，产生了CD9缺失小鼠，并且它们看起来很健康。目前正在进行进一步的研究。