Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival
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 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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The p38 pathway has been reported to interfere with ERK activity during apoptosis.
“The p38 pathway has been reported to interfere with ERK activity during apoptosis (see 88 for review); thus, ERK activity was assayed in these genotypes by measuring phospho-ERK levels.”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [88]
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- Authors
- Junttila, M. R., Li, S., & Westermarck, J.
- Affiliations
- Åbo Akademi University (FI)
- University of Helsinki (FI)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2007-11-26
- Volume
- 22
- Issue
- 4
- Pages
- 954-965
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2003060606
- Cited by
- 826
- References
- 138
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 24 · 2023: 19 · 2022: 32 · 2021: 48 · 2020: 28 · 2019: 36 · 2018: 42 · 2017: 41 · 2016: 58 · 2015: 49 · 2014: 76 · 2013: 72 · 2012: 74
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- ERK signaling, phosphatase, protein phosphatase 2A, apoptosis, cell survival
- MeSH terms
- Animals, Cell Survival, Humans, Models, Biological, Phosphoprotein Phosphatases, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System
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