Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway
Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway
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DOI：
10.1128/mcb.25.1.336-345.2005
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发表时间：
2005-01-01
影响因子：
5.3
通讯作者：
Tournier, C
中科院分区：
文献类型：
--
作者：
Wang, X;Merritt, AJ;Tournier, C
为了阐明MEK 5在体内的生理意义，我们已经检查了小鼠中mek 5基因消除的效果。杂合子小鼠看起来是健康的并且是可生育的。然而，mek 5（-/-）胚胎在大约胚胎日龄10.5（E10.5）时死亡。mek 5（-/-）胚胎的表型包括心脏发育异常，以及在心脏，头部和背侧区域的突变胚胎的增殖显着减少和细胞凋亡增加。MEK 5的缺乏不影响细胞周期进程，但使小鼠胚胎成纤维细胞（MEF）对山梨醇增强半胱天冬酶3活性的能力敏感。对mek 5（-/-）MEFs的进一步研究表明，MEK 5是介导细胞外信号调节激酶5（ERK 5）激活和调节肌细胞增强因子2转录活性所必需的。总的来说，这是第一项严格确定MEK 5在体内作为ERK 5激活剂和作为正常胚胎发育所需的细胞存活的重要调节剂的作用的研究。
To elucidate the physiological significance of MEK5 in vivo, we have examined the effect of mek5 gene elimination in mice. Heterozygous mice appear to be healthy and were fertile. However, mek5(-/-) embryos die at approximately embryonic day 10.5 (E10.5). The phenotype of the mek5(-/-) embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos. The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity. Further studies with mek5(-/-) MEFs indicate that MEK5 is required for mediating extracellular signal-regulated kinase 5 (ERK5) activation and for the regulation of the transcriptional activity of myocyte enhancer factor 2. Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development.