EGFR forms ligand-independent oligomers that are distinct from the active state

Patrick O. Byrne, Kalina Hristova, Daniel J Leahy

Research output: Contribution to journalArticlepeer-review


The human epidermal growth factor receptor (EGFR/ERBB1) is a receptor tyrosine kinase (RTK) that forms activated oligomers in response to ligand. Much evidence indicates that EGFR/ERBB1 also forms oligomers in the absence of ligand, but the structure and physiological role of these ligand-independent oligomers remain unclear. To examine these features, we use fluorescence microscopy to measure the oligomer stability and FRET efficiency for homo- and hetero-oligomers of fluorescent protein-labeled forms of EGFR and its paralog, human epidermal growth factor receptor 2 (HER2/ERBB2) in vesicles derived from mammalian cell membranes. We observe that both receptors form ligand-independent oligomers at physiological plasma membrane concentrations. Mutations introduced in the kinase region at the active state asymmetric kinase dimer interface do not affect the stability of ligand-independent EGFR oligomers. These results indicate that ligand-independent EGFR oligomers form using interactions that are distinct from the EGFR active state.

Original languageEnglish (US)
Pages (from-to)13353-13362
Number of pages10
JournalThe Journal of biological chemistry
Issue number38
StatePublished - Sep 18 2020


  • EGFR
  • epidermal growth factor receptor
  • fluorescence resonance energy transfer
  • FRET
  • membrane protein
  • oligomerization
  • receptor tyrosine kinase
  • signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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