| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The small GTPase M-Ras, which we have identified recently, induces neuronal differentiation in PC12 cells. We examined signal transduction pathways responsible for the differentiation. M-Ras is involved in the cAMP-induced differentiation. M-Ras was activated by cAMP-GEF, which is activated by cAMP, and then induced the activation of the transcription factor CREB. Consequently, this differentiation pathway is : cAMP → cAMP-GEF → M-Ras → ? → CREB. This pathway is distinct from those in which Ras and Papl are involved. Since CREB is essential for the long-term memory, M-Ras might participate in the regulation of higher-order brain functions including the long-term memory. To assess this possibility by generating M-Ras gene knockout mice, we constructed M-Ras gene targeting vector. We also identified target proteins for M-Ras by yeast two-hybrid system. These include Nore 1 and Rgl, which are regarded as target proteins for Ras. We are investigating whether these proteins participate in the target proteins for Ras. We are investigating whether these proteins participate in the CREB-induced neuronal differentiation.
RhoD induced disassembly of the stress fibers and focal adhesions and suppressed cell migration in cultured cells. It also interfered with cytokinesis but not with nuclear division, resulting in multinucleation in cultured cells and Xenopus embryos. These phenomena were brought about by antagonization of RhoD to RhoA. We identified by two-hybrid system RhoD-binding proteins, some of which were target proteins for RhoA. The results suggest that RhoD antagonizes RhoA by sequestering the target proteins for RhoA. We further cloned Tc10 and the novel Rho family protein, RhoT, both of which were highly expressed in muscle tissues and caused microspike formation. We are examining their roles in muscle cell differentiation.
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