ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1
ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1
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DOI：
10.1038/35074516
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发表时间：
2001-05-01
影响因子：
21.3
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Harada, T;Morooka, T;Nishida, E
经典的丝裂原活化蛋白激酶（MAPK;也称为细胞外信号调节激酶），ERK级联已被证明在细胞增殖和分化中具有至关重要的作用。在PC 12细胞中，神经生长因子（NGF）诱导ERK的持续激活对神经元分化至关重要。然而，对于神经元分化至关重要的ERK的下游靶点尚未确定。在这里，我们表明，神经生长因子诱导强，持续表达p35，神经元特异性激活剂的细胞周期蛋白依赖性激酶5（Cdk 5），通过激活ERK途径。Cdk 5的诱导激酶活性是NGF诱导的神经突生长所必需的。我们的研究结果表明，ERK的持续激活是必要的和足够的p35的强诱导。此外，转录因子Egr 1由NGF通过ERK途径诱导，并介导ERK对p35的诱导。因此，我们的研究结果定义了一个重要的信号通路，下游的ERK/MAPK，导致神经元分化。
The classical mitogen-activated protein kinase (MAPK; also known as extracellular-signal-regulated kinase), ERK cascade has been shown to have a crucial role in cell proliferation and differentiation. In PC12 cells, sustained activation of ERK induced by nerve-growth factor (NGF) is essential for neuronal differentiation. However downstream targets of ERK that are essential for neuronal differentiation have not been defined. Here we show that NGF induces strong, sustained expression of p35, the neuron-specific activator of cyclin-dependent kinase 5 (Cdk5), through activation of the ERK pathway. The induced kinase activity of Cdk5 is required for NGF-induced neurite outgrowth. Our results indicate that sustained activation of ERK is necessary and sufficient for strong induction of p35. Furthermore, the transcription factor Egr1, is induced by NGF through the ERK pathway and mediates induction of p35 by ERK. Our results thus define an essential signalling pathway, downstream of ERK/MAPK, that leads to neuronal differentiation.