| Project/Area Number |
11480214
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cell biology
|
|---|
| Research Institution | Osaka University (2000)
Kurume University (1999) |
|---|
Principal Investigator |
MEKADA Eisuke Research Institute for Microbial Diseases, Osaka University, Professor, 微生物病研究所, 教授 (20135742)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
|
|---|
| Keywords | LPA / HB-EGF / Transactivation / G-oritein-coupled receptors / Ectodomain shedding / エクトドメインシェディング / プロテインキナーゼC / MAPキナーゼキナーゼ / リゾフォスファチジン酸 / メタロプロテアーゼ |
|---|
| 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.
|
