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Digital signaling and hysteresis characterize ras activation in lymphoid cells

Jayajit Das1, Mary Ho, Julie Zikherman

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

Cell
|January 27, 2009
PubMed

Insights

Lymphocyte Ras activation exhibits digital signaling through SOS feedback, enabling cellular memory. Complementary analog and digital pathways convert input signals into distinct cellular outputs.

Area of Science:

  • Cellular biology
  • Molecular signaling

Background:

  • Ras protein activation is crucial for cell function.
  • RasGRP and SOS are key molecules activating Ras in lymphocytes.

Purpose of the Study:

  • To investigate the role of feedback regulation in SOS-mediated Ras activation.
  • To understand how analog and digital pathways on Ras convert input signals.

Main Methods:

  • In silico and in vitro studies were integrated.
  • Analysis of the dose-response curve and feedback loop of SOS.

Main Results:

  • A positive feedback loop in SOS enhances Ras activation, leading to digital signaling.
  • SOS feedback creates hysteresis, enabling sustained Ras activation and cellular memory.
  • Ras activation via RasGRP alone shows analog signaling.

Conclusions:

  • Complementary analog (RasGRP) and digital (SOS) pathways efficiently convert analog input to digital output in lymphocytes.
  • Feedback regulation of SOS is critical for digital signaling and cellular memory in lymphocytes.
  • Findings predict impacts on lymphocyte function and development.

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