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

Melissa R Junttila1, Song-Ping Li, Jukka Westermarck

  • 1Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|November 28, 2007
PubMed

Insights

Stress-activated JNK/p38 kinases suppress the ERK pathway during apoptosis. This review details JNK/p38-mediated inhibition of ERK, focusing on phosphatases, to understand cell fate decisions in apoptosis.

Area of Science:

  • Cellular and Molecular Biology
  • Signal Transduction Pathways
  • Apoptosis Research

Background:

  • Mitogen-activated protein kinase (MAPK) pathways regulate critical cellular processes including growth, differentiation, and apoptosis.
  • The extracellular signal-regulated kinase (ERK) pathway is traditionally viewed as survival-promoting, counteracting proapoptotic pathways like c-Jun NH(2)-terminal kinase (JNK)/p38 MAPK.
  • Emerging evidence indicates JNK/p38 kinases actively suppress ERK activity during apoptosis induction.

Purpose of the Study:

  • To review mechanisms by which JNK/p38 kinases negatively regulate the ERK pathway.
  • To highlight the role of phosphatases (PP2A, MKPs) as key inhibitors of ERK activity in apoptosis.
  • To propose a model where ERK pathway inhibition is central to cellular decisions regarding survival or death.

Main Methods:

  • Literature review and synthesis of current research on MAPK signaling in apoptosis.
  • Focus on phosphatase-mediated inhibition of ERK.
  • Development of a conceptual model for ERK pathway regulation in cell fate determination.

Main Results:

  • JNK/p38 kinases employ specific mechanisms to inhibit ERK pathway activity during apoptosis.
  • Phosphatases, including PP2A and MAPK phosphatases (MKPs), are identified as crucial negative regulators of ERK.
  • The suppression of ERK by JNK/p38 is positioned as a critical control point in apoptosis signaling.

Conclusions:

  • Negative regulation of the ERK pathway by JNK/p38 kinases is a key event in the decision-making process of apoptosis.
  • Understanding these inhibitory mechanisms, particularly involving phosphatases, is vital for comprehending cell survival and death.
  • Dysregulation of ERK pathway inhibition may have implications for physiological and pathological conditions, including cellular transformation.

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