| Project/Area Number |
21591199
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | National Center for Geriatrics and Gerontology (2010-2011)
Nagoya University (2009) |
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Principal Investigator |
KATSUMI Akira 独立行政法人国立長寿医療研究センター, 輸血管理室, 医長 (80378025)
|
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| Co-Investigator(Kenkyū-buntansha) |
KAIBUCHI Kozo 名古屋大学, 大学院・医学系研究科, 教授 (00169377)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 血液内科学 / 細胞接着 / Rho family / 急性白血病 / GAP / Rac / RhoH / GEF / Rho / 抗接着治療 |
|---|
| Research Abstract |
Rho GTPases have been widely studied because they are critical regulators of cellularsignaling mediated by G-protein-coupled receptors, tyrosine kinase receptors and integrins. RhoH, a member of the Rho family, is specifically expressed in the hematopoietic cells, including bone marrow progenitor, differentiated myeloid andlymphoid cells. RhoH antagonizes Rac, however, the molecules that inactivate Racdownstream of RhoH have not been identified. Here we perform GTP-RhoH affinity column chromatography. Using triple quadrupole liquid chromatography tandemmass spectrometer, 83 different proteins associated with active RhoH were identified. They include Rho GTPase activating proteins(RhoGAP), serine/threonine kinases, phosphatidylinositol kinases, and others. Among them, focused on T-cell activationRhoGTPaseactivatingprotein(TAGAP), whichisspecweifically expressed inthe hematopoietic cells. TAGAP binds to RhoH through its GAP domain. Expression of both full length and GAP domain of TAGAP effectively deactivates Rac, whereas GAP domain deleted TAGAP did not. These results suggest that RhoH negatively regulates Rac through TAGAP.
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