Journal Article

High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Krall, Jordan A., MacBeath, Gavin, Beyer, Elsa M.

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Activation / Affinity / Apoptosis / Binding / Biology / Cell adhesion & migration / Cell growth / Cell Line / Computer applications / Epidermal growth factor / Epidermal growth factor receptors / Epidermal growth factors / Humans / Infrared imaging systems / Kinases / Ligands / Localization / Mathematical models / Phospholipase / Phospholipase C / Phospholipase C gamma - metabolism / Phosphorylation / Protein Binding / Proteins / Receptor mechanisms / Receptor, Epidermal Growth Factor - metabolism / Receptors / Signal Transduction / Signaling / STAT Transcription Factors - metabolism / Transcription factors / Transducers / Trends