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Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes

Arup K Chakraborty1, Jayajit Das, Julie Zikherman

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

Science Signaling
|April 16, 2009
PubMed

Insights

Lymphocyte activation relies on Ras proteins. A positive feedback loop in Son of Sevenless (SOS) creates digital "on/off" signaling, enabling T cell memory.

Area of Science:

  • Cellular signaling pathways
  • Molecular mechanisms of immune response

Background:

  • Ras proteins are key regulators of cellular functions.
  • Ras-GRP and Son of Sevenless (SOS) activate Ras in lymphocytes.

Framework:

  • A positive feedback loop involving Ras binding to SOS creates allosteric regulation.
  • This feedback loop drives digital (on/off) signaling in lymphocytes.

Implementation:

  • In silico and in vitro studies demonstrate the role of SOS allosteric regulation.
  • The SOS feedback loop induces hysteresis in dose-response curves.

Implications:

  • Digital signaling mediated by SOS may enable T cell memory.
  • Complementary analog (Ras-GRP) and digital (SOS) pathways efficiently convert analog input to digital output.
  • Digital signaling is crucial for lymphocyte function and development.

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