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Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation

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Gompel, M. | Soulie, C. | Ceballos-Picot, I. | Meijer, L.

Edité par CCSD ; Karger -

In the presence of retinoic acid undifferentiated NT2 cells turn into terminally differentiated hNT (or NT2N) neurons within 5 weeks. We have used this in vitro cellular model to investigate the changes in expression and activity of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) during this neuronal differentiation process. We here show that CDK1/2 protein level and kinase activity sharply decrease during the NT2-->hNT transition. In contrast, the activity of CDK5/p35 dramatically increases, probably as a result of an enhanced expression of p35 in a stable CDK5 level background. GSK-3 activity increases modestly during the differentiation of hNT cells, and this event correlates with enhanced expression of each of the three GSK-3 isoforms. Pharmacological inhibitors of CDKs and GSK-3 lead to a dose-dependent decrease in cell viability.

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