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家庭增长因素的成员。 HB-EGF（ProHB-EGF）的膜锚定形式不仅是HB-EGF的可溶性形式的前体，而且是生物活性分子的前体。前EGF与其他膜蛋白形成复合物。 CD9和乙酰硫酸盐蛋白聚糖与ProHB-EGF相关并调节其生物学活性。 ProHB-EGF还与IntegrinalPha3Beta1形成复合物。免疫荧光染色的研究表明，由ProHB-EGF，CD9和IntileminalPha3Beta1组成的复合物在细胞细胞接触位点共定位，这表明前egf络合物在juxtacrine方式中在细胞间通信中起着作用。为了了解ProHB-EGF复合物在细胞间交流中的生理作用，我们进行了以下研究，并获得了以下结果：1）CD9CD9上调ProHB-EGF活性的上调上调了ProHB-EGF的生物学活性。确定了上调所需的CD9和ProHB-EGF的区域。2）ProHB-EGFWE的生长抑制活性，已经观察到，在培养条件下，ProHB-EGF在可溶性HB-EGF和EGF的培养条件下显示出生长的抑制活性。刺激细胞生长。因此，有人建议可溶性形式和膜锚定形式具有不同的生物学活性来进行细胞生长控制。3）CD9 NULL MICECD9的分析将具有将ProHB-EGF与Intirinallinalpha3beta1连接起来的关键作用。为了分析ProHB-EGF复合物CD9 NULL小鼠的生理作用。 CD9 NULL小鼠出生并看起来很健康，但在生殖系统中显示出严重的缺陷。现在正在进行进一步的研究。