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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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 血栓止血 / インテグリン / シグナル伝達 / 血小板 / 血栓･止血学 |
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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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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Agonist stimulation, talin-1, and kindlin-3 are crucial for αIIbβ3 activation in a human megakaryoblastic cell line, CMK2013
Author(s)
Nakazawa T, Tadokoro S, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y.
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Journal Title
Exp Hematol.
Volume: 41(1)
Issue: 1
Pages: 79-90
DOI
Related Report
Peer Reviewed
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[Journal Article] Mcl-1 and Bcl-xL regulate Bak/Bax-dependent apoptosis of the megakaryocytic lineage at multistages.2012
Author(s)
Kodama T, Hikita H, Kawaguchi T, Shigekawa M, Shimizu S, Hayashi Y, Li W, Miyagi T, Hosui A, Tatsumi T, Kanto T, Hiramatsu N, Kiyomizu K, Tadokoro S, Tomiyama Y, Hayashi N, Takehara T.
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Journal Title
Cell Death Differ.
Volume: 19(11)
Issue: 11
Pages: 1856-1869
DOI
Related Report
Peer Reviewed
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[Presentation] Agonist stimulation, talin-1, and kindlin-3 are crucial for αIIbβ3 activation in a human megakaryoblastic cell line, CMK.2011
Author(s)
Nakazawa T, Tadokoro S, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Tomiyama Y, Kanakura Y.
Organizer
The American Society of Hematology 53rd Annual meeting
Place of Presentation
San Diego, USA
Related Report
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[Presentation] Agonist stimulation, talin-1, and kindlin-3 are crucial for αIIbβ3 activation in a human megakaryoblastic cell line, CMK.2011
Author(s)
Nakazawa T, Tadokoro S, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Tomiyama Y, Kanakura Y.
Organizer
Special Symposium on the Basic Science, The American Society of Hematology 53rd Annual meeting
Place of Presentation
San Diego, USA
Related Report
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