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

HB-EGF是EGF家族中的一员。HB-EGF的膜锚定形式（proHB-EGF）也已知是白喉毒素受体。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博士在细胞培养基中鉴定了HB-EGF，并研究了HB-EGF可溶形式的生物活性，而Mekada则研究了作为白喉毒素受体的proHB-EGF。本次联合会议的目的是研究proHB-EGF在细胞生长和发育过程中的生理作用。CD 9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α 3 β 1形成复合物。通过免疫荧光染色的研究表明，由proHB-EGF、CD 9和整合素3 β 1组成的复合物共定位于细胞-细胞接触部位，这表明 ...更多信息 proHB-EGF复合物在细胞间通讯中以阿曲他克林的方式起作用。为了了解proHB-EGF复合物在细胞间通讯中的生理作用，我们进行了以下研究，结果如下：1）CD 9：CD 9上调proHB-EGF活性，上调proHB-EGF的生物学活性，确定了CD 9和proHB-EGF上调所必需的区域。2）proHB-EGF的生长抑制活性：我们已经观察到，在HB-EGF和EGF的可溶形式刺激细胞生长的培养条件下，proHB-EGF通过阿托克林机制显示出生长抑制活性。因此，这表明可溶性形式和膜锚定形式具有不同的细胞生长控制的生物活性。3）CD 9裸小鼠的分析：CD 9将具有连接proHB-EGF与整合素α 3 β 1的关键作用。为了分析proHB-EGF复合物的生理作用，产生了CD 9缺失小鼠。CD 9基因敲除小鼠出生时看起来健康，但表现出严重的生殖系统缺陷。目前正在进行进一步的研究。少

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