The role and molecular mechanism of the ectodomain shedding of HB-EGF
The role and molecular mechanism of the ectodomain shedding of HB-EGF
批准号:
11480214
负责人:
MEKADA Eisuke
金额:
$9.79万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000
中文摘要
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英文摘要
The ectodomain of the transmembrane form of HB-EGF (proHB-EGF) is cleaved at the cell surface by proteases, yielding a soluble growth factor. A number of stimuli including TPA and calcium ionophore accelerate this cleavage. However, proHB-EGF is shed constitutively under normal culture conditions without any particular stimuli. In this study we showed that constitutive cleavage resulted largely from factor (s) contained in supplemented FCS in a culture medium. Analysis of serum factors using monkey kidney-derived Vero cells revealed that lysophosphatidic acid is a major factor in FCS for stimulation of proHB-EGF shedding. Signaling mechanism downstream of LPA was also studied. Analysis including several dominant negative and constitutively active mutants or pharmacological inhibitors revealed Ras-MAPK cascade is critical for LPA-induced shedding of proHB-EGF.
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Yu,X.,etc: "Integrin-dependent EGF Receptor Activation at cell-cell Contact Sites."J.Cell Sci.. 113. 2139-2147 (2000)
Yu,X.,等:“细胞-细胞接触位点的整合素依赖性 EGF 受体激活。”J.Cell Sci.. 113. 2139-2147 (2000)
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Tsuneoka, M.and Mekada, E.: "Ras/MEX signaling suppresses Myc-dependent apoptosis in cells transformed by c-myc and activated ras."Oncogene. 19. 115-123 (2000)
Tsuneoka, M. 和 Mekada, E.:“Ras/MEX 信号传导抑制由 c-myc 转化并激活 ras 的细胞中 Myc 依赖性细胞凋亡。”癌基因。
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Tsuneoka,M.: "Ras/MEK signaling suppresses Mycdependent apoptosis in cells transformed by c-myc and activated ras."Oncogene. (in press).
Tsuneoka,M.:“Ras/MEK 信号传导抑制 c-myc 转化的细胞中 Myc 依赖性细胞凋亡并激活 ras。”癌基因。
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Nakamura, K., Mitamura, T., Takahashi, T., Kobayashi, T.and Mekada, E.: "Importance of the Major Extracellular Domain of CD9 and the EGF-like Domain of HB-EGF for Upregulation of Binding and Activity."J.Biol.Chem.. 275. 18284-18290 (2000)
Nakamura, K.、Mitamura, T.、Takahashi, T.、Kobayashi, T. 和 Mekada, E.:“CD9 的主要细胞外结构域和 HB-EGF 的 EGF 样结构域对于上调结合和活性的重要性
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Miyado, K., Yamada, G., Yamada, S., Hasuwa, H., Nakamura, Y., Ryu, F., Suzuki, K., Kosai, K., Inoue, K., Ogura, A., Okabe, M.and Mekada, E.: "Requirement of CD9 on the egg plasma membrane for fertilization."Science. 287. 321-324 (2000)
Miyado, K.、Yamada, G.、Yamada, S.、Hasuwa, H.、Nakamura, Y.、Ryu, F.、Suzuki, K.、Kosai, K.、Inoue, K.、Ogura, A.、
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