Analysis of the comprising membrane-anchored growth factor and cell adhesion molecule.

包含膜锚定生长因子和细胞粘附分子的分析。

• 批准号: 07458192
• 负责人: MEKADA Eisuke
• 金额: $ 4.74万
• 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458192/
• 关键词: juxtacrine; integrin; HB-EGF; CD9; TM4; heparansulfate proteoglycans; membrane-anchored growth factors; DRAP27; CD63; ジフテリア毒素リセプター; TPA

We have found that the membrane-anchored form of heparin-binding EGF-like growth factor (proHB-EGF) forms a complex with CD9 and integrin alpha3bl. The final goal of this study is to understand the physiological role of this complex and the mode of action of juxtacrine growth factors. we have done several experiments and obtained the following results.(1) Localization of the complexVero cell, derived from monkey kidney, was studied by immunofluorescence using specific antibodies to proHB-EGF,CD9, integrin alpha3, and integrin beta1. The results revealed that proHB-EGF,CD9 and integrin alpha3b1 localized at cell-cell junction region.(2) The role of heparin-binding domain (HBD)To analyze the role of HBD domain of proHB-EGF,the deletion mutants of HBD of proHB-EGF were produced. The results showed that HBD is not essential for the mitogenic activity and diphtheria toxin binding activity.(3) Expression of CD9 in myelinImmunohistochemical studies showed that CD9 is expressed in myelin of human central and peripheral nervous systems. The expression of ProHB-EGF was not detected in myelin.

我们发现肝素结合egf样生长因子（proHB-EGF）的膜锚定形式与CD9和整合素alpha3bl形成复合物。本研究的最终目的是了解该复合物的生理作用和近分泌生长因子的作用模式。我们做了几次实验，得到了以下结果。(1)利用proHB-EGF、CD9、整合素α 3和整合素β 1特异性抗体，利用免疫荧光技术研究了从猴肾中提取的复合物vero细胞的定位。结果显示，proHB-EGF、CD9和整合素alpha3b1定位于细胞-细胞交界区。(2)肝素结合结构域（HBD）的作用为分析HBD结构域在proHB-EGF中的作用，制备了proHB-EGF HBD缺失突变体。结果表明，HBD对有丝分裂活性和白喉毒素结合活性不是必需的。(3) CD9在髓鞘中的表达免疫组织化学研究表明，CD9在人中枢和周围神经系统的髓鞘中表达。髓磷脂中未检测到ProHB-EGF的表达。

项目成果

Shishido, Y.: "Heparin-like molecules on the cell surface potentiate binding of diphtheria toxin to the diphtheria toxin receptor/membrane-anchored heparin-binding EGF-like growth factor." J.Biol.C. 270. 29578-29585 (1995)

Shishido, Y.：“细胞表面的类肝素分子增强了白喉毒素与白喉毒素受体/膜锚定的肝素结合 EGF 样生长因子的结合。”

Tsuneoka,M.: "c-myc activates RCC1 gene expression through E-box elements." Oncogene. (in press).

Tsuneoka,M.：“c-myc 通过 E-box 元件激活 RCC1 基因表达。”

Higashiyama,S.: "The membrane protein CD9/DRAP27 potentiates the growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF)." J.Cell Biol.128. 929-938 (1995)

Higashiyama,S.：“膜蛋白 CD9/DRAP27 增强膜锚定肝素结合 EGF 样生长因子 (HB-EGF) 的生长因子活性。”

Mitamura,T.: "Diphtheria toxin binds to the EGF-like domain of human heparin-binding EGF-like growth factor/diphtheria toxin receptor, and inhibits specifically its mitogenic activity." J.Biol.Chem.270. 1015-1019 (1995)

Mitamura,T.：“白喉毒素与人肝素结合 EGF 样生长因子/白喉毒素受体的 EGF 样结构域结合，并特异性抑制其促有丝分裂活性。”

Tsuneoka, M.: "c-myc activates RCC1 gene expression through E-box elements." Oncogene.(in press).

Tsuneoka, M.：“c-myc 通过 E-box 元件激活 RCC1 基因表达。”