2000 Fiscal Year Final Research Report Summary
The role and molecular mechanism of the ectodomain shedding of HB-EGF
| Project/Area Number |
11480214
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Osaka University (2000)
Kurume University (1999) |
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Principal Investigator |
MEKADA Eisuke Research Institute for Microbial Diseases, Osaka University, Professor, 微生物病研究所, 教授 (20135742)
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| Co-Investigator(Kenkyū-buntansha) |
UMADA Toshiyuki Institute of Life Science and Research Center for Innovative Cancer Therapy, Kurume University, Assistant, 分子生命科学研究所, 助手 (30213482)
MIYADO Kenji Research Institute for Microbial Diseases, Osaka University, Assistant, 微生物病研究所, 助手 (60324844)
IWAMOTO Ryo Research Institute for Microbial Diseases, Osaka University, Instructor, 微生物病研究所, 講師 (10213323)
TSUNEOKA Makoto Institute of Life Science and Research Center for Innovative Cancer Therapy, Kurume University, Assistant Professor, 分子生命科学研究所, 助教授 (50197745)
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| Project Period (FY) |
1999 – 2000
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| Keywords | LPA / HB-EGF / Transactivation / G-oritein-coupled receptors / Ectodomain shedding |
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| Research Abstract |
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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[Publications] 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)
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「研究成果報告書概要(欧文)」より
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[Publications] Baba, I., Shirasawa, S., Iwamoto, R., Okumura, K., Tsunoda, T., Nishioka, M., Fukuyama, K., Yamamoto, K., Mekada, E.and Sasazuki, T.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Res. 60. 6886-6889 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Saeki, K., Suzuki, H., Tsuneoka, M., Maeda, M., Iwamoto, R., Hasuwa, H., Shida, S., Takahashi, T., Sakaguchi, M., Endo, T., Miura, Y., Mckada, E.and Mihara, K.: "Identification of mammalian Tom22 as a subunit of the preprotein translocase of the mitochondrial outer membrane."J.Biol.Chem.. 275. 31996-32002 (2000)
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「研究成果報告書概要(欧文)」より
