| 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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| 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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