MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm
MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm
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DOI：
10.1016/j.bbrc.2010.01.097
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发表时间：
2010-03-05
影响因子：
3.1
通讯作者：
Shima, Hiroshi
中科院分区：
文献类型：
--
作者：
Masuda, Kouhei;Katagiri, Chiaki;Shima, Hiroshi
MAPK磷酸酶-7（MKP-7）被鉴定为JNK特异性磷酸酶。然而，尽管其对JNK的高度特异性，MKP-7也与ERK相互作用。我们先前表明，作为它们相互作用的生理结果，活化的ERK在Ser-446磷酸化MKP-7，并稳定MKP-7。在本研究中，我们分析了MKP-7在ERK激活中的功能。时程实验表明，MKP-7及其磷酸酶死亡突变体均延长了有丝分裂原诱导的ERK磷酸化，表明MKP-7可作为ERK的支架。一个重要的免疫组织学发现是PMA刺激后磷酸化ERK的核转位被共表达的MKP-7阻断，此外，磷酸化ERK与MKP-7共定位于细胞质中。报告基因分析表明，MKP-7阻断ERK介导的转录。总体而言，我们的数据表明，MKP-7下调ERK依赖性基因的表达，通过阻断磷酸化ERK的核积累。(C)2010年爱思唯尔公司All rights reserved.
MAPK phosphatase-7 (MKP-7) was identified as a JNK-specific phosphatase. However, despite its high specificity for JNK, MKP-7 interacts also with ERK. We previously showed that as a physiological consequence of their interaction, activated ERK phosphorylates MKP-7 at Ser-446, and stabilizing MKP-7. In the present study, we analyzed MKP-7 function in activation of ERK. A time-course experiment showed that both MKP-7 and its phosphatase-dead mutant prolonged mitogen-induced ERK phosphorylation, suggesting that MKP-7 functions as a scaffold for ERK. An important immunohistological finding was that nuclear translocation of phospho-ERK following PMA stimulation was blocked by co-expressed MKP-7 and, moreover, that phospho-ERK co-localized with MKP-7 in the cytoplasm. Reporter gene analysis indicated that MKP-7 blocks ERK-mediated transcription. Overall, our data indicate that MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK. (C) 2010 Elsevier Inc. All rights reserved.