| Project/Area Number |
12460039
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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 |
応用微生物学・応用生物化学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUKUI Yasuhisa Grad. Sch. Agriculture and Life Science, The University of Tokyo, Professor, 大学院・農学生命科学研究科, 教授 (00181248)
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| Co-Investigator(Kenkyū-buntansha) |
IHARA Sayoko Grad. Sch. Agriculture and Life Science, The University of Tokyo, Assistant, 大学院・農学生命科学研究科, 助手 (80292788)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | phosphoinositides / PH domain / GEF / PIP_3 / Rac / Ruffling / signal transduction / growth factors / ホスファチジルイノシトール3キナーゼ / 核移行 / グアニンヌクレオチド交換因子 / GTPase促進活性因子 / ラッフル膜 / Gタンパク質 / 核外輸送 |
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| Research Abstract |
We have explored the roles of PIP_3 binding proteins, especially on Swap-70 protein, in order to understand the signal transduction of phosphatidylinositol 3-kinase (PI3K).
Swap-70 has been identified as a ubiquitous distribution suggested its other functions. Our study revealed that Swap-70 moved to the membrane ruffles after stimulation with growth factors and that this protein was a guanine nucleotide exchange factor (GEE) for Rac. This GEF activity was refused for signaling from growth factor receptors to Rac via PI3K. Kidney cell cultures established from Swap-70 deficient mice showed impaired membrane ruffling after EGF stimulation compared with those for wild type mice.
Swap-70 contains a DH domain, which exhibits the GEF activity, and a PH domain responsible for PIP3 binding. The PH domain binds to the DH domain to inhibit the GEF activity. This binding was abolished to PIP_3, suggestion that PIP_3 releases the DH domain from the inhibitory effect of the PH domain.
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