BMP enhances transcriptional responses to NGF during PC12 cell differentiation

被引:17
作者
Lönn, P [1 ]
Zaia, K [1 ]
Israelsson, C [1 ]
Althini, S [1 ]
Usoskin, D [1 ]
Kylberg, A [1 ]
Ebendal, T [1 ]
机构
[1] Uppsala Univ, Biomed Ctr, Dept Neurosci, SE-75123 Uppsala, Sweden
关键词
cluster analysis; Egr; immediate early genes; Jun; microtubule-associated protein 1b; neurite outgrowth;
D O I
10.1007/s11064-005-6868-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bone morphogenetic proteins (BMPs) enhance neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells. To investigate the mechanism of this potentiating effect, real-time PCR was used to analyze the expression of 45 selected genes. A robust increase in expression of 10 immediate early genes including Egr1-4, Hes1, Junb, Jun and Fos was observed already after 1 h treatment with NGF alone. NGF plus BMP4 further increased these transcripts at 1 h and activated 18 additional genes. BMP4 alone induced Smad6, Mtap1b and Hes1. Egr3 was the gene most strongly upregulated by NGF and BMP4. However, luciferase assays showed that the cloned Egr3 proximal promoter was not involved in the BMP4 potentiation. Blocking Egr3 and Junb function by dominant-negative constructs reduced neurite outgrowth under stimulating conditions, proving that activation of members of both the Egr and Jun families is necessary for maximal PC12 cell response to NGF and BMP4.
引用
收藏
页码:753 / 765
页数:13
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