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- Title
Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival.
- Authors
Junttila, Melissa R.; Song-Ping Li; Westermarck, Jukka
- Abstract
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 NH2-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).
- Subjects
MITOGEN-activated protein kinases; PHOSPHATASES; CELLULAR signal transduction; CELL growth; JNK mitogen-activated protein kinases; APOPTOSIS
- Publication
FASEB Journal, 2008, Vol 22, Issue 4, p954
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.06-7859rev