Cited by 827Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

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

Junttila, Melissa R., Li, Song‐Ping, Westermarck, Jukka·2008·The FASEB Journal

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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Crossref · 10.1096/fj.06-7859rev

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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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