Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation
Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation
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DOI：
10.1159/000076567
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发表时间：
2004-01-01
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影响因子：
--
通讯作者：
Meijer, L
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文献类型：
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作者：
Gompel, M;Soulié, C;Meijer, L
在维甲酸存在下，未分化的NT2细胞在5周内转化为终末分化的HNT(或NT2N)神经元。我们利用这一体外细胞模型研究了细胞分化过程中细胞周期蛋白依赖性蛋白激酶(CDKs)和糖原合成酶-3(GSK-3)表达和活性的变化。我们在这里显示CDK1/2蛋白水平和激酶活性在NT2-->；HNT转变过程中急剧下降。相反，CDK5/p35的活性显著增加，这可能是由于在稳定的CDK5水平背景下p35表达增强的结果。在HNT细胞分化过程中，GSK-3活性略有升高，这一事件与三种GSK-3亚型中的每一种亚型的表达增强有关。CDKs和GSK-3的药物抑制剂会导致细胞存活率的剂量依赖性下降。版权所有(C)2004 S.Karger AG，巴塞尔。
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. Copyright (C) 2004 S. Karger AG, Basel.