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Differential regulation of HSP70 expression by the JNK kinases SEK1 and MKK7 in mouse embryonic stem cells treated with cadmium
Author(s) -
Nishitai Gen,
Matsuoka Masato
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21743
Subject(s) - p38 mitogen activated protein kinases , kinase , phosphorylation , mapk/erk pathway , transfection , hsp70 , microbiology and biotechnology , chemistry , protein kinase a , heat shock protein , biology , biochemistry , gene
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 CdCl 2 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 CdCl 2 exposure, the phosphorylation of JNK, p38, and ERK was suppressed in sek1 −/− mkk7 −/− cells. When sek1 −/− or mkk7 −/− cells were treated with CdCl 2 , 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 CdCl 2 ‐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 CdCl 2 ‐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 CdCl 2 . J. Cell. Biochem. 104: 1771–1780, 2008. © 2008 Wiley‐Liss, Inc.