2013 Fiscal Year Final Research Report
Development of new therapy based on a molecular mechanism of integrin activation signaling via integrin activation complex
| Project/Area Number |
23591416
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 大阪大学, 大学院医学系研究科, 助教 (80403062)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Yoshiaki 大阪大学, 医学部附属病院, 准教授 (80252667)
KANAKURA Yuzuru 大阪大学, 大学院医学系研究科, 教授 (20177489)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 血栓止血 / インテグリン / シグナル伝達 / 血小板 |
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| Research Abstract |
We characterized the functional regulation of endogenously expressed aIIbb3 in a megakaryoblastic cell line, CMK. We firstly demonstrated that PAR1 induced transient aIIbb3 activation in CMK. Stable talin-1 or kindlin-3 knockdown cells confirmed that the PAR1-induced aIIbb3 activation was dependent on talin-1 and kindlin-3 expression. Transient overexpression of full-length talin or talin-head domain (THD) alone did not activate aIIbb3, but required agonist stimulation. Kindlin-3 overexpression significantly augmented agonist-induced aIIbb3 activation. The head-rod interaction was critical for auto-inhibition of talin-1, and the interaction between the THD and the membrane-proximal region of the b3 was essential for aIIbb3 activation. In addition, THD and kindlin-3 cooperatively augmented PAR1 induced aIIbb3 activation (Exp Hematol. 2013). We further demonstrated that the ILK-PINCH-parvin complex plays an important role and supports integrin activation (PLoS One. 2013).
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Research Products
(18 results)
