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Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance

Edita Aksamitiene1, Anatoly Kiyatkin, Boris N Kholodenko

  • 1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.

Biochemical Society Transactions
|January 21, 2012
PubMed

Insights

The phosphoinositide 3-kinase (PI3K)/Akt and Ras/mitogen-activated protein kinase (MAPK) pathways exhibit context-dependent cross-talk, influencing each other

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Systems biology

Background:

  • The phosphoinositide 3-kinase (PI3K)/Akt and Ras/mitogen-activated protein kinase (MAPK) pathways are critical regulators of cell growth, proliferation, and survival.
  • Interactions between these two major signaling cascades are known to occur, but the precise nature and context-dependency of this cross-talk remain incompletely understood.

Purpose of the Study:

  • To elucidate the multifaceted cross-talk between the PI3K/Akt and Ras/MAPK signaling pathways.
  • To investigate how this cross-talk is influenced by varying extracellular cues and growth factor concentrations.
  • To understand the functional implications of pathway interactions for cellular signal processing.

Main Methods:

  • Integration of experimental data with computational simulations.
  • Analysis of signaling dynamics under different conditions of pathway activation.

Main Results:

  • Demonstration of bidirectional cross-talk where PI3K/Akt can activate MAPK, and MAPK can inhibit PI3K/Akt.
  • Identification of context-dependency: PI3K activation of MAPK is prominent at low growth factor doses, while MAPK inhibition of PI3K is significant at high doses.
  • Evidence that pathway cross-talk enhances cellular capabilities for decoding complex extracellular signals.

Conclusions:

  • The PI3K/Akt and Ras/MAPK pathways engage in complex, context-specific cross-talk.
  • This intricate interplay allows cells to dynamically process and integrate signals from multiple receptors.
  • Understanding pathway cross-talk is crucial for comprehending cellular responses to diverse environmental stimuli.

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