High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways

PLoS One. 2011 Jan 10;6(1):e15945. doi: 10.1371/journal.pone.0015945.


Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • ErbB Receptors / metabolism*
  • Humans
  • Ligands
  • Phospholipase C gamma / metabolism
  • Protein Binding
  • STAT Transcription Factors / metabolism
  • Signal Transduction*


  • Ligands
  • STAT Transcription Factors
  • ErbB Receptors
  • Phospholipase C gamma