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

膜锚定的HB-EGF对细胞生长的作用

• 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

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。因此该蛋白一方面是一种膜锚定生长因子，另一方面是细菌毒素的特异性受体。 Klagsbrun 博士鉴定了细胞培养基中的 HIB-EGF，并研究了可溶形式 HB-EGF 的生物活性，而 Mekada 则研究了 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 integrincalpha3beta1 形成复合物。免疫荧光染色研究表明，由 proHB-EGF、CD9 和 integrina#3beta1 组成的复合物共定位于细胞-细胞接触位点，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 在可溶形式的 HB-EGF 和 EGF 刺激细胞生长的培养条件下通过邻分泌机制显示出生长抑制活性。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学活性。3)CD9缺失小鼠的分析：CD9在连接proHB-EGF和整合素α3β1方面起关键作用。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。较少的

项目成果

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