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P19 EC細胞の神経分化におけるMAPキナーゼシステムの役割：王宏, 大西素子, 田村眞理（東北大・加齢研・遺伝子情報）

Roles of MAP kinase in P19 EC Cell Neural differentiation : Hong WANG, Motoko OHNISHI, Shinri TAMURA ( Department of Biochemistry, Institute of Development, Aging, and Cancer, Tohoku University )

P19 embryonal carcinoma cells have been used as a model system for studying early embryonic development and differentiation. P19 EC cells in aggregation culture with a relatively high concentration of retinoic acid ( RA ) followed by monolayer culture can differentiate into neural cells. The signaling pathway responsible for this neural differentiation remains unclear. In the present study, we addressed the roles of MAP kinase pathways in RA-induced P19 EC cell neural differentiation. In order to induce neural differentiation, P19 EC cells were cultured on bacterial grade dishes to form aggregates, termed embryoid bodies, for 4 days in presence of 1μ M RA and then replated on tissue culture grade dishes and culture for 3 more days without RA. During the differentiation, the activities of JNK and ERK increased, but p38 activity did not alter. OA treatment of the cells markedly suppressed neural differentiation and caused a reduced JNK activity. OA treatment increased ERK activity but had no effect on p38 activity. To further assess the role of MAP kinase pathway in RA-induced neural differentiation, we tested the effect of MEK inhibitor and p38 inhibitor on differentiation. Treatment of the cells with neither of these two inhibitors had any effect on neural diferentiation. These results suggest that JNK pathway but not that of ERK or p38 plays an importment role in neural differentiation.