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Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival

来自 ResearchGate

阅读量：

284

作者：

MR Junttila，SP Li，J Westermarck

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摘要：

Mitogen-activated protein kinase (MAPK) pathways constitute a large modular network that regulates a variety of physiological processes, such as cell growth, differentiation, and apoptotic cell death. The function of the ERK pathway has been depicted as survival-promoting, in essence by opposing the proapoptotic activity of the stress-activated c-Jun NH(2)-terminal kinase (JNK)/p38 MAPK pathways. However, recently published work suggests that extracellular regulated kinase (ERK) pathway activity is suppressed by JNK/p38 kinases during apoptosis induction. In this review, we will summarize the current knowledge about JNK/p38-mediated mechanisms that negatively regulate the ERK pathway. In particular, we will focus on phosphatases (PP2A, MKPs) as inhibitors of ERK pathway activity in regulating apoptosis. A model proposed in this review places the negative regulation of the ERK pathway in a central position for the cellular decision-making process that determines whether cells will live or die in response to apoptosis-promoting signals. In addition, we will discuss the potential functional relevance of negative regulation of ERK pathway activity, for physiological and pathological conditions (e.g., cellular transformation).

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关键词：

Animals Humans Mitogen-Activated Protein Kinases Cell Survival MAP Kinase Signaling System Phosphoprotein Phosphatases Models, Biological

DOI：

10.1096/fj.06-7859rev

被引量：

1220

年份：

2008

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