Rhodes James, Lutka Frances A, Jordan-Sciutto Kelly L, Bowser Robert
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Neuroreport. 2003 Mar 3;14(3):449-52. doi: 10.1097/00001756-200303030-00030.
The molecular mechanisms by which neurotrophins such as nerve growth factor (NGF) induce neurite outgrowth and differentiation remain unclear, although multiple intracellular signaling pathways are known to participate. Recent studies have shown that nuclear transcription factors play an important role in NGF-stimulated neuritic outgrowth in PC12 cells. We investigated whether FAC1, a novel transcriptional regulator that exhibits altered subcellular distribution during brain development, is responsive to NGF-induced neurite outgrowth of PC12 cells. Our studies demonstrate that NGF induces a rapid, transient increase in FACI mRNA that is dependent upon ERK activation, and that FAC1 protein exhibits altered subcellular distribution during neurite outgrowth. These findings suggest that FAC1 expression and subcellular localization are regulated by NGF signaling pathways during neurite outgrowth.
尽管已知多种细胞内信号通路参与其中,但神经营养因子如神经生长因子(NGF)诱导神经突生长和分化的分子机制仍不清楚。最近的研究表明,核转录因子在PC12细胞中NGF刺激的神经突生长中起重要作用。我们研究了FAC1,一种在脑发育过程中表现出亚细胞分布改变的新型转录调节因子,是否对PC12细胞中NGF诱导的神经突生长有反应。我们的研究表明,NGF诱导FACI mRNA快速、短暂增加,这依赖于ERK激活,并且FAC1蛋白在神经突生长过程中表现出亚细胞分布改变。这些发现表明,在神经突生长过程中,FAC1的表达和亚细胞定位受NGF信号通路调节。