Analysis of the ectodomain shedding mechanism of HB-EGF
| Project/Area Number |
16207014
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
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Principal Investigator |
MEKADA Eisuke Osaka University, Research Institute for Microbial Disease, Professor, 微生物病研究所, 教授 (20135742)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Ryo Osaka University, Research Institute for Microbial Disease, Associate Professor, 微生物病研究所, 助教授 (10213323)
MIZUSHIMA Hiroto Osaka University, Research Institute for Microbial Disease, Research Associate, 微生物病研究所, 助手 (30379094)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥51,090,000 (Direct Cost: ¥39,300,000、Indirect Cost: ¥11,790,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
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| Keywords | HB-EGF / ectodomain shedding / protease / ADAM / エクトドメインシェディング / シグナル伝達 |
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| Research Abstract |
Ectodomain shedding is critical process for the action of heparin-binding EGF-like growth factor (HB-EGF). This process is regulated by a number of extracellular stimuli and intracellular signaling molecules. However, the molecular mechanism for ectodomain shedding has largely remained to be clarified. We found the following results :
1)Over-expression of ADAM12 mutant form with defective metalloprotease domain induced ectodomain shedding of HB-EGF in Vero cells. Over-expression of several mutant forms of ADAM12 and co-precipitation experiments with anti-ADAM12 tag antibody suggested that ADAM12 may contribute to HB-EGF shedding as an adapter protein for signaling, rather than as a protease.
2)Screening of low molecular-weight chemicals which possess the inhibitory activity for HB-EGF ectodomain shedding was performed. A few compounds showed the inhibitory activity. Further characterization is underway.
3)To understand the molecules which are involved in ectodomain shedding of HB-EGF, we constructed a screening strategy which enables to identify genes necessary for the shedding. To do this, siRNA library containing 8.4 k human genome sequence was constructed and transfected in human cells by retro virus vecter system. Cell populations which did not respond to the stimuli for shedding were isolated.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Cytoplasmic Domain Phosphorylation of Heparin-Binding EGF-like Growth Factor.2006
Author(s)
Wang, X., Mizushima, H., Adachi, S., Oishi, M., Iwamoto, R., Mekada, E.
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Journal Title
Cell Struct.Funct. (in press.)
NAID
Related Report
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[Journal Article] Clinical significance of heparin-binding epidermal growth factor-Like growth factor in peritoneal fluid of ovarian cancer.2005
Author(s)
Yagi, H., Miyamoto, S., Tanaka, Y., Sonoda, K., Kobayashi, H., Kishikawa, T., Iwamoto, R., Mekada, E., Nakano, H.
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Journal Title
Brit.J.Cancer 92
Pages: 1737-1745
Related Report
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[Journal Article] Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.2005
Author(s)
Shirakata, Y., Kimura, K., Nanba, D., Iwamoto, R., Tokumaru, S., Morimoto, C., Yokota, K., Nakamura, M., Sayama, K., Mekada, E., Higashiyama, S., Hashimoto, K.
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Journal Title
J.Cell Sci. 118
Pages: 2363-2370
Related Report
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[Journal Article] Clinical significance of heparin-binding EGF (epidermal growth factor)-like growth factor and ADAM (a disintegrin and metalloprotease) 17 expression in human ovarian cancer.2005
Author(s)
Tanaka, T., Miyamoto, S., Suzuki, S.O., Oki, E., Yagi, H., Sonoda, K., Yamazaki, A., Mizushima, H., Maehara, Y., Mekada, E., Nakano, H.
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Journal Title
Clin.Cancer Res. 11
Pages: 4783-4792
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