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Related Experiment Videos

Autocrine loops with positive feedback enable context-dependent cell signaling.

S Y Shvartsman1, M P Hagan, A Yacoub

  • 1Department of Chemical Engineering, Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

American Journal of Physiology. Cell Physiology
|February 8, 2002
PubMed
Summary

Autocrine loops enable context-dependent cell signaling by modulating intracellular dynamics. Extracellular conditions and ligand recapture influence signaling duration, impacting cellular responses to stimuli like radiation.

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Area of Science:

  • Cellular Biology
  • Systems Biology
  • Biophysics

Background:

  • Cell signaling pathways, such as the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) pathways, are crucial for cellular responses.
  • Autocrine signaling, where cells release ligands that act on themselves, involves positive feedback loops that can influence signaling dynamics.
  • The extracellular environment's composition can significantly alter intracellular signaling responses to external stimuli.

Purpose of the Study:

  • To elucidate a mechanism for context-dependent cell signaling mediated by autocrine loops with positive feedback.
  • To investigate how extracellular medium composition influences intracellular signaling dynamics.
  • To develop a mathematical model for studying autocrine loop functions.

Main Methods:

Related Experiment Videos

  • Developed a mathematical model incorporating ligand release, transport, binding, and intracellular signaling dynamics.
  • Studied the epidermal growth factor receptor (EGFR) system, focusing on the Ras-MAPK pathway and ligand-releasing proteases.
  • Analyzed context-dependent signaling responses in human carcinoma cells exposed to ionizing radiation.

Main Results:

  • Autocrine loops with positive feedback mediate context-dependent cell signaling.
  • Extracellular medium composition critically influences intracellular signaling dynamics (e.g., MAPK activation amplitude and duration).
  • Ligand recapture efficiency determines whether signaling responses are short-lived or prolonged/persistent.

Conclusions:

  • Context-dependent signaling arises from dynamic interactions within autocrine loops.
  • Autocrine loops can serve as modules for context-dependent cell signaling in growth factor and cytokine systems.
  • The model provides a framework for interpreting experimental observations of context-dependent cellular responses.