| Project/Area Number |
22248030
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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 |
Applied animal science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HAKUNO Fumihiko 東京大学, 大学院農学生命科学研究科, 助教 (30282700)
NISHIHARA Masugi 東京大学, 大学院農学生命科学研究科, 教授 (90145673)
ITO Akihiro 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
YASUSHI Saeki 公益財団法人東京都医学総合研究所, 吉田化学遺伝学研究室, 主席研究員 (80462779)
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| Project Period (FY) |
2010-05-31 – 2013-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥46,020,000 (Direct Cost: ¥35,400,000、Indirect Cost: ¥10,620,000)
Fiscal Year 2012: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2011: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2010: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
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| Keywords | 代謝・内分泌制御 / インスリン様成長因子 / インスリン受容体基質 / ユビキチン化酵素 / 脱ユビキチン化酵素 / 細胞内シグナル / インスリン様活性 / ユビキチンリガーゼ / アダプタータンパク質 / インスリン / インスリン様成長因子受容体 / 増殖 |
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| Research Abstract |
Insulin receptor substrates (IRSs) that are phosphorylated by insulin-like growth factor (IGF)-I receptor tyrosine kinases. Phosphotyrosyl IRSs are recognized by signaling molecules possessing SH2 domains, which mediate various IGF bioactivities. However, we have shown that IRSs are also associated with other proteins by a phosphotyrosine-independent mechanism. These protein complexes contain a number of ubiquitin ligases (E3) and deubiquitinating enzymes (DUBs). Our results indicate that ubiquitination of IRSs which was dynamically regulated by these E3 and DUBs in response to other extracellular factor, plays important roles not only in regulation of their protein levels but also modulation of their tyrosine phosphorylation, leading to control of IGF bioactivities, such as a growth-promoting activity.
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