Development of new therapy based on a molecular mechanism of integrin activation signaling via integrin binding proteins
| Project/Area Number |
20591152
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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 | Osaka University |
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Principal Investigator |
TADOKORO Seiji Osaka University, 医学系研究科, 助教 (80403062)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Yoshiaki 大阪大学, 医学部附属病院, 講師 (80252667)
KANAKURA Yuzuru 大阪大学, 医学系研究科, 教授 (20177489)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インテグリン / シグナル伝達 / α-actinin / 血小板 |
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| Research Abstract |
We report here a new role for α-actinin, which links the cytoplasmic domains of integrin β tails, in inside-out integrin activation. In resting human platelets, α-actinin was associated with αIIbβ3, while inside-out signaling from protease-activated receptors (PARs) dephosphorylated and dissociated α-actinin from αIIbβ3. Overexpression of wild-type α-actinin inhibited PAR-induced initial αIIbβ3 activation in the human megakaryoblastic cell line, CMK. In contrast, knockdown of α-actinin augmented PAR-induced αIIbβ3 activation. Furthermore wild-type α-actinin, but not the mutant Y12F α-actinin, normalized the augmented αIIbβ3 activation in α-actinin shRNA transduced CMK. These observations suggest that α-actinin might play a potential role in setting integrins to a low-affinity ligand-binding state in resting platelets and regulating αIIbβ3 activation via inside-out signaling (Tadokoro S, et al. A potential role for α-actinin in inside-out αIIbβ3 signaling. Blood. 2011 Jan 6 ; 117(1) : 250-258).
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Report
(4 results)
Research Products
(38 results)
