Requirement of p38 mitogen-activated protein kinase for neuronal differentiation in PC12 cells
Requirement of p38 mitogen-activated protein kinase for neuronal differentiation in PC12 cells
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DOI：
10.1074/jbc.273.38.24285
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发表时间：
1998-09-18
影响因子：
4.8
通讯作者：
Nishida, E
中科院分区：
文献类型：
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作者：
Morooka, T;Nishida, E
神经生长因子（NGF）诱导经典MAP激酶持续活化尽管先前的研究表明ERK/MAPK的持续激活对于细胞的神经元分化是重要的，最近的报道显示，单独抑制ERK/MAPK活化的持续期不能阻断由NGF引起的神经突生长。这些结果表明在神经元分化中需要由NGF触发的额外信号传导途径。在这里，我们表明，神经生长因子诱导持续激活的p38，MAPK超家族的一个亚家族成员，和抑制p38通路阻断PC 12细胞中的神经突生长。令人惊讶的是，组成型活性MAPK/ERK激酶（MAPKK，也称为MEK）的表达导致p38活化以及ERK/MAPK活化，并且p38抑制剂阻断由组成型活性MAPK/MEK引起的神经突生长。此外，当与EGF治疗组合时，p38的组成型活化能够诱导神经突生长。这些结果揭示了p38在PC 12细胞神经元分化中的重要作用。
Nerve growth factor (NGF) induces sustained activation of classical MAP kinase (MAPK, also known as ERK) and neuronal differentiation in PC12 cells, whereas epidermal growth factor (EGF) induces transient activation of ERK/MAPK and stimulates proliferation of the cells, Although previous studies showed that sustained activation of ERK/MAPK is important for neuronal differentiation of the cells, a recent report revealed that inhibition of the sustained phase of ERK/MAPK activation alone does not block neurite outgrowth caused by NGF. These results suggest requirement for an additional signaling pathway(s) triggered by NGF in neuronal differentiation. Here we show that NGF induces sustained activation of p38, a subfamily member of the MAPK superfamily, and that inhibition of the p38 pathway blocks neurite outgrowth in PC12 cells. Surprisingly, expression of constitutively active MAPK/ERK kinase (MAPKK, also known as MEK) results in p38 activation as well as ERK/MAPK activation, and a p38 inhibitor blocks neurite outgrowth caused by the constitutively active MAPK/MEK, Moreover, constitutive activation of p38 is able to induce neurite outgrowth when combined with EGF treatment. These results reveal an essential role of p38 in neuronal differentiation in PC12 cells.