PTEN Suppression Promotes Neurite Development Exclusively in Differentiating PC12 Cells via PI3-Kinase and MAP Kinase Signaling
PTEN Suppression Promotes Neurite Development Exclusively in Differentiating PC12 Cells via PI3-Kinase and MAP Kinase Signaling
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DOI：
10.1002/jcb.22867
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发表时间：
2010-12-15
影响因子：
4
通讯作者：
Zhang, Xia
中科院分区：
文献类型：
--
作者：
Jia, Lintao;Ji, Shaoping;Zhang, Xia
作为一种催化磷脂酰肌醇和蛋白质底物去磷酸化的双特异性磷酸酶，PTEN在神经系统发育中起着至关重要的作用。然而，PTEN在神经突生长中的调节作用仍存在争议，其下游信号事件也尚不明确。在此，我们发现当大鼠嗜铬细胞瘤PC12细胞暴露于神经生长因子（NGF）时，PTEN的敲低促进了细胞的增殖和存活，但不促进神经突生长。相反，在表达巢蛋白的分化型PC12细胞中选择性沉默PTEN则显著促进了神经突的伸长。在PTEN敲低后，Akt和Erk1/2磷酸化水平的升高参与了NGF诱导的PC12细胞神经突发育的加速。通过在PC12细胞中内源性PTEN沉默后恢复表达一种脂质磷酸酶缺陷型PTEN突变体，确定了PTEN的脂质磷酸酶和蛋白质磷酸酶活性在神经突发育中的不同作用，以及受这些磷酸酶活性影响的详细分子特征。我们的研究表明，PTEN在神经突发育中总体上具有抑制作用，这与该磷酸酶在PC12细胞分化起始中可能不可或缺的作用相协调。《细胞生物化学杂志》111: 1390 - 1400, 2010。（C）2010威利 - 利斯公司
As a dual-specificity phosphatase catalyzing the dephosphorylation of phosphatidylinositols and protein substrates, PTEN is critically involved in the nervous system development. However, the regulatory role of PTEN in neurite outgrowth is still controversial, and the downstream signaling events remain elusive. Here, we show that PTEN knockdown promoted the proliferation and survival but not the neurite outgrowth of rat pheochromocytoma PC12 cells when exposed to nerve growth factor (NGF). In contrast, selective PTEN silencing in differentiating PC12 cells that express nestin significantly facilitated neurite elongation. Elevated Akt and Erk1/2 phosphorylation was involved in accelerated NGF-induced neurite development of PC12 cells following PTEN knockdown. Discriminated roles of the lipid phosphatase and protein phosphatase activities of PTEN in neurite development, as well as the detailed molecular profiles affected by these phosphatase activities, were defined by restored expression of a lipid phosphatase-deficient PTEN mutant following endogenous PTEN silencing in PC12 cells. Our study suggests an overall inhibitory effect of PTEN in neurite development reconciled by a probably indispensable role of this phosphatase in the initiation of PC12 cell differentiation. J. Cell. Biochem. 111: 1390-1400, 2010. (C) 2010 Wiley-Liss, Inc.