Ndrg4 enhances NGF-Induced ERK activation uncoupled with Elk-1 activation

被引:20
作者
Hongo, S [1 ]
Watanabe, T [1 ]
Takahashi, K [1 ]
Miyazaki, A [1 ]
机构
[1] Showa Univ, Sch Med, Dept Biochem, Shinagawa Ku, Tokyo 1428555, Japan
关键词
Ndrg4; ERK signaling pathway; Elk-1; serum response element; microtubules; NGF; PC12; cells;
D O I
10.1002/jcb.20763
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
Ndrg4 is expressed predominantly in the early postnatal rat brain and may be related to neural cell differentiation. PC12 cell lines stably expressing increased levels of Ndrg4 protein display enhanced NGF-induced phosphorylation of MEK and ERK. In contrast, the Ndrg4-C2-overexpressed PC12 cell lines showed attenuated NGF-promoted phosphorylation of Elk-1, which is a nuclear target of ERK. A reporter assay also indicated that Ndrg4-C2 suppresses Elk-1-mediated transcriptional activation and SRE reporter expression. The suppressive effect of Ndrg4-C2 on NGF-induced activation of Elk-1 was abolished by colchicine but not by cytochalasin D, suggesting that microtubules are involved in the reduced activation of Elk-1 by Ndrg4. Ndrg4 may play a role in supporting the activation of ERK and its target proteins needed for neuronal differentiation and in reducing the activation of Elk-1 implicated in cell growth.
引用
收藏
页码:185 / 193
页数:9
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