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。另一只手的受体。膜蛋白。建议...更多的ProHB-EGF复合物在细胞间交流中播放前细胞的交流，我们进行了以下研究，并获得了以下结果：1）CD9上的ProHB-EGF活动上调确定了CD9和proHB-EGF必要的前期的prohb-egf.区域的生物学活性。2）ProHB-EGF的生长抑制活性：我们已经观察到prohb-egf表现出通过juxtacrine机制，培养条件，培养条件，培养条件显示出生长抑制性的生长抑制。 HB-EGF和EGF的溶液形式刺激细胞生长。伴随着Prohb-complex 9零小鼠的thysiolololelecal作用

项目成果

Kagawa, T: "Immune system-related CD9 is expressed in mouse central nervous system myelin at a very late stage of myelination." J. Neurosci. Res.50. 312-320 (1997)

Kakawa, T：“免疫系统相关的 CD9 在髓鞘形成的晚期阶段在小鼠中枢神经系统髓磷脂中表达。”

Tsuneoka, M.: "c-myc activates RCCI gene expression through E-box elements." Oncogene. 14. 2301-2311 (1997)

Tsuneoka, M.：“c-myc 通过 E-box 元件激活 RCCI 基因表达。”

Izumi, Y: "A metalloprotease-disintegrin, MDC9/Meltring-g/ADM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-Like growth factor." EMBO J.17. 7260-7272 (1998)

Izumi, Y：“金属蛋白酶解整合素、MDC9/Meltring-g/ADM9 和 PKCd 参与 TPA 诱导的膜锚定肝素结合 EGF 样生长因子的胞外域脱落。”

Tsuneoka, M.: "N-myc transactivates RCCI gene expression in rat fibroblast cells transformed by N-myc and v-ras." J. Biochem.124. 1013-1019 (1998)

Tsuneoka, M.：“N-myc 反式激活 N-myc 和 v-ras 转化的大鼠成纤维细胞中的 RCCI 基因表达。”

岩本 亮: "医学&サイエンスシリーズ 細胞接着のしくみと疾患" 羊土社, 7 (1998)

岩本亮：《医学与科学系列细胞粘附机制与疾病》Yodosha，7 (1998)