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EGF-dependent re-routing of vesicular recycling switches spontaneous phosphorylation suppression to EGFR signaling

Martin Baumdick1, Yannick Brüggemann1,2, Malte Schmick1

  • 1Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Elife
|November 27, 2015
PubMed

Insights

Epidermal growth factor receptor (EGFR) activation is tightly regulated. A new study shows ligand-induced trafficking suppresses spontaneous EGFR activation while preserving signaling capacity.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Receptor biology

Background:

  • Epidermal growth factor receptor (EGFR) activation is crucial for cellular responses but prone to spontaneous, spurious signaling.
  • Protein tyrosine phosphatases (PTPs) regulate EGFR activity, balancing signal fidelity with response diversity.

Purpose of the Study:

  • To investigate how ligand-mediated EGFR trafficking suppresses spontaneous activation while maintaining signal transduction.
  • To elucidate the role of receptor ubiquitination and trafficking dynamics in regulating EGFR signaling.

Main Methods:

  • Investigated EGFR monomer and dimer dynamics using biochemical assays.
  • Utilized cell-based assays to track EGFR trafficking and ubiquitination.
  • Examined the impact of PTP1B activity on EGFR localization and signaling.

Main Results:

  • Unliganded EGFR monomers are protected from spontaneous activation via recycling through PTP1B-rich perinuclear regions.
  • EGF binding triggers EGFR ubiquitination and self-association, switching trafficking from suppressive recycling to directional transport.
  • Receptor transit time to late endosomes, regulated by ubiquitination, determines signal termination by PTP1B.

Conclusions:

  • A ubiquitin-mediated switch in EGFR trafficking dynamically regulates receptor signaling.
  • This mechanism effectively suppresses spurious EGFR activation without compromising responsiveness to epidermal growth factor (EGF).
  • The findings reveal a sophisticated regulatory strategy for maintaining cellular signaling homeostasis.
Keywords:
autocatalysiscell biologycomputational biologynonepartitioned phosphatase activitiesrecycling endosomespontaneous phosphorylationsystems biologyubiquitinationvesicular EGFR trafficking

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