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首页> 外文期刊>Journal of cell biology >Activation of Nuclear Factor 魏b and bcl-x Survival Gene Expression by Nerve Growth Factor Requires Tyrosine Phosphorylation of I魏B伪
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Activation of Nuclear Factor 魏b and bcl-x Survival Gene Expression by Nerve Growth Factor Requires Tyrosine Phosphorylation of I魏B伪

机译：神经生长因子激活核因子魏布和bcl-x生存基因表达的激活需要酪氨酸磷酸化I魏Bα

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NGF has been shown to support neuron survival by activating the transcription factor nuclear factor-魏B (NF魏B). We investigated the effect of NGF on the expression of Bcl-xL, an anti鈥揳poptotic Bcl-2 family protein. Treatment of rat pheochromocytoma PC12 cells, human neuroblastoma SH-SY5Y cells, or primary rat hippocampal neurons with NGF (0.1鈥?0 ng/ml) increased the expression of bcl-xL mRNA and protein. Reporter gene analysis revealed a significant increase in NF魏B activity after treatment with NGF that was associated with increased nuclear translocation of the active NF魏B p65 subunit. NGF-induced NF魏B activity and Bcl-xL expression were inhibited in cells overexpressing the NF魏B inhibitor, I魏B伪. Unlike tumor necrosis factor-伪 (TNF-伪), however, NGF-induced NF魏B activation occurred without significant degradation of I魏Bs determined by Western blot analysis and time-lapse imaging of neurons expressing green fluorescent protein鈥搕agged I魏B伪. Moreover, in contrast to TNF-伪, NGF failed to phosphorylate I魏B伪 at serine residue 32, but instead caused significant tyrosine phosphorylation. Overexpression of a Y42F mutant of I魏B伪 potently suppressed NFG-, but not TNF-伪鈥搃nduced NF魏B activation. Conversely, overexpression of a dominant negative mutant of TNF receptor-associated factor-6 blocked TNF-伪鈥? but not NGF-induced NF魏B activation. We conclude that NGF and TNF-伪 induce different signaling pathways in neurons to activate NF魏B and bcl-x gene expression.
机译：NGF已显示可通过激活转录因子核因子-魏布（NF魏B）支持神经元存活。我们研究了NGF对抗凋亡Bcl-2家族蛋白Bcl-xL表达的影响。用NGF（0.1'？0 ng / ml）处理大鼠嗜铬细胞瘤PC12细胞，人成神经细胞瘤SH-SY5Y细胞或原代大鼠海马神经元可增加bcl-xL mRNA和蛋白的表达。记者基因分析显示，NGF治疗后NF魏布活性显着增加，这与活性NF魏布p65亚基的核转运增加有关。 NGF诱导的NF魏B活性和Bcl-xL表达在过量表达NF魏B抑制剂I魏Bα的细胞中受到抑制。但是，与肿瘤坏死因子-α（TNF-α）不同，通过Western印迹分析和表达绿色荧光蛋白的带有标记的I魏的神经元的延时成像确定，NGF诱导的NF魏B激活发生时，I魏B没有明显降解。 Bα。而且，与TNF-α相反，NGF不能使丝氨酸残基32处的I魏Bα磷酸化，而是引起明显的酪氨酸磷酸化。 I魏Bα的Y42F突变体的过表达有效地抑制了NFG-，而不是TNF-α诱导的NF魏B的活化。相反，TNF受体相关因子6的显性负突变体的过表达阻断了TNF-α-β。但不是NGF诱导的NF魏B活化。我们得出的结论是，NGF和TNF-α在神经元中诱导不同的信号通路来激活NF魏B和bcl-x基因表达。

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