Differential regulation of HSP70 expression by the JNK kinases SEK1 and MKK7 in mouse embryonic stem cells treated with cadmium
Differential regulation of HSP70 expression by the JNK kinases SEK1 and MKK7 in mouse embryonic stem cells treated with cadmium
复制标题
DOI：
10.1002/jcb.21743
复制
发表时间：
2008-08
影响因子：
4
通讯作者：
G. Nishitai;M. Matsuoka
中科院分区：
文献类型：
--
作者：
G. Nishitai;M. Matsuoka
JNK是丝裂原活化蛋白激酶（MAPK）的一员，在环境应激时被MAPK激酶SEK 1和MKK 7激活。在本研究中，氯化镉处理MAPK磷酸化和HSP 70表达的影响进行了研究，在小鼠胚胎干细胞（ES）缺乏sek 1基因，mkk 7基因，或两者兼而有之。CdCl 2暴露后，JNK、p38和ERK的磷酸化在sek 1 −/− mkk 7 −/−细胞中受到抑制。当sek 1-/-或mkk 7-/-细胞用CdCl 2处理时，JNK磷酸化显着减少，但p38或ERK的磷酸化却没有减少，而在sek 1-/-细胞中观察到p38磷酸化的微弱减少。因此，SEK 1和MKK 7都是JNK磷酸化所必需的，而它们在p38和ERK磷酸化中的作用可能与另一种激酶的作用重叠。我们还观察到CdCl 2诱导的HSP 70表达在sek 1 −/− mkk 7 −/−细胞中被消除，在sek 1 −/−细胞中减少，在mkk 7 −/−细胞中增强。类似地，热休克因子1（HSF 1）的磷酸化在sek 1 −/− mkk 7 −/−和sek 1 −/−细胞中减少，但在mkk 7 −/−细胞中增加。转染JNK 1、JNK 2、p38α、ERK 1或ERK 2特异性siRNA可抑制CdCl 2诱导的HSP 70表达。相反，p38β或p38γ的沉默导致HSP 70蛋白的进一步积累。这些结果表明，在CdCl 2处理的小鼠ES细胞中，SEK 1通过不同的MAPK亚型上调HSP 70表达，MKK 7通过不同的MAPK亚型下调HSP 70表达。J.细胞。104：1771-1780，2008.© 2008 Wiley利斯公司
JNK, a member of the mitogen‐activated protein kinases (MAPKs), is activated by the MAPK kinases SEK1 and MKK7 in response to environmental stresses. In the present study, the effects of CdCl2 treatment on MAPK phosphorylation and HSP70 expression were examined in mouse embryonic stem (ES) cells lacking the sek1 gene, the mkk7 gene, or both. Following CdCl2 exposure, the phosphorylation of JNK, p38, and ERK was suppressed in sek1−/− mkk7−/− cells. When sek1−/− or mkk7−/− cells were treated with CdCl2, JNK phosphorylation, but not the phosphorylation of either p38 or ERK, was markedly reduced, while a weak reduction in p38 phosphorylation was observed in sek1−/− cells. Thus, both SEK1 and MKK7 are required for JNK phosphorylation, whereas their role in p38 and ERK phosphorylation could overlap with that of another kinase. We also observed that CdCl2‐induced HSP70 expression was abolished in sek1−/− mkk7−/− cells, was reduced in sek1−/− cells, and was enhanced in mkk7−/− cells. Similarly, the phosphorylation of heat shock factor 1 (HSF1) was decreased in sek1−/− mkk7−/− and sek1−/− cells, but was increased in mkk7−/− cells. Transfection with siRNA specific for JNK1, JNK2, p38α, ERK1, or ERK2 suppressed CdCl2‐induced HSP70 expression. In contrast, silencing of p38β or p38γ resulted in further accumulation of HSP70 protein. These results suggest that HSP70 expression is up‐regulated by SEK1 and down‐regulated by MKK7 through distinct MAPK isoforms in mouse ES cells treated with CdCl2. J. Cell. Biochem. 104: 1771–1780, 2008. © 2008 Wiley‐Liss, Inc.