| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥720,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
We demonstrated previously that FGFRs and EphA4 trans-activate each other by forming a heterodimer, and augment downstream signals through FRS2α, a major docking protein of FGFRs, and MAP kinase. Based on these studies, I have studied the interaction domains among EphA4, FGFRs and FRS2α, and trans-phosphorylation partners of the two receptor tyrosine kinases. EphA4 interacts directly with and phosphorylates not only FGFRs but also FRS2α. From these interaction studies, it has become clear that EphA4, FGFR and FRS2α compose a ternary complex, which plays an important role in proliferation and differentiation of neural stem cells. Furthermore, I also found that FGFR directly activates ephexin1, a downstream molecule of EphA4, which regulates migration and morphological changes of neuronal cells through activation of Rho family. These studies show that the interaction of EphA4 with FGFR functions as a molecular mediator for neural cell proliferation, migration and differentiation.
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