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The Dark Side of Cell Signaling: Positive Roles for Negative Regulators

Mark A Lemmon1, Daniel M Freed1, Joseph Schlessinger1

  • 1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cancer Biology Institute, West Haven, CT 06516, USA.

Cell
|March 12, 2016
PubMed

Insights

Negative regulators in cell signaling do more than just stop signals; they enhance control. This study reveals how these regulators, receptor internalization, and rapid molecular cycles refine cellular responses.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Cell signaling typically focuses on positive responses to stimuli.
  • Negative regulators are often viewed solely as signal terminators.
  • The precise roles of negative regulators in fine-tuning signaling are less understood.

Purpose of the Study:

  • To explore the multifaceted roles of negative regulators in cell signaling.
  • To investigate how negative regulators enhance signaling control and specificity.
  • To re-evaluate the concept of signal termination in cellular processes.

Main Methods:

  • Analysis of signaling pathways downstream of cell-surface receptors.
  • Examination of receptor internalization dynamics.
  • Study of rapid enzymatic cycles (kinase/phosphatase, GTP/GDP).

Main Results:

  • Negative regulators actively contribute to enhancing cell-signaling control.
  • Receptor internalization modulates signaling specificity.
  • Rapid molecular cycles (e.g., kinase/phosphatase, GTP/GDP) boost responsiveness and enable kinetic proofreading.

Conclusions:

  • Negative regulators are crucial for sophisticated signal control, not just termination.
  • Signal termination can be viewed as a switch to a new cellular state.
  • Understanding these mechanisms provides deeper insights into cellular information processing.

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