Interactions between Ligand-Bound EGFR and VEGFR2

J Mol Biol. 2021 Jun 25;433(13):167006. doi: 10.1016/j.jmb.2021.167006. Epub 2021 Apr 20.

Abstract

In this work, we put forward the provocative hypothesis that the active, ligand-bound RTK dimers from unrelated subfamilies can associate into heterooligomers with novel signaling properties. This hypothesis is based on a quantitative FRET study that monitors the interactions between EGFR and VEGFR2 in the plasma membrane of live cells in the absence of ligand, in the presence of either EGF or VEGF, and in the presence of both ligands. We show that direct interactions occur between EGFR and VEGFR2 in the absence of ligand and in the presence of the two cognate ligands. However, there are not significant heterointeractions between EGFR and VEGFR2 when only one of the ligands is present. Since RTK dimers and RTK oligomers are believed to signal differently, this finding suggests a novel mechanism for signal diversification.

Keywords: EGFR; VEGFR2; cell signaling; heterooligomers; receptor tyrosine kinases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Cell Membrane / metabolism*
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fluorescence Resonance Energy Transfer
  • HEK293 Cells
  • Humans
  • Ligands
  • Protein Binding
  • Protein Multimerization
  • Signal Transduction*
  • Spectrometry, Fluorescence
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / chemistry
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Ligands
  • Vascular Endothelial Growth Factor A
  • Epidermal Growth Factor
  • ErbB Receptors
  • Vascular Endothelial Growth Factor Receptor-2