Predominance of activated EGFR higher-order oligomers on the cell surface

Andrew H A Clayton, Suzanne G. Orchard, Edouard C. Nice, Richard G Posner, Antony W. Burgess

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) kinase is generally considered to be activated by either ligand-induced dimerisation or a ligand-induced conformational change within pre-formed dimers. We report the relationship between ligand-induced higher-order EGFR oligomerization and EGFR phosphorylation on the surface of intact cells. We have combined lifetime-detected Forster resonance energy transfer, as a probe of the receptor phosphorylation state and image correlation spectroscopy, to extract the relative association state of activated versus unactivated EGFR, to determine the ratio of the average number of receptors for active (phosphorylated) and inactive clusters. There are at least four times as many receptors in the ligand-induced active clusters than inactive clusters. Contrary to the prevailing view that the EGFR dimer is the predominant, active form, our data determine that higher-order EGFR oligomers are the dominant species associated with the ligand activated EGFR tyrosine kinase.

Original languageEnglish (US)
Pages (from-to)316-324
Number of pages9
JournalGrowth Factors
Volume26
Issue number6
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Oligomers
Epidermal Growth Factor Receptor
Ligands
Phosphorylation
Dimers
Oligomerization
Fluorescence Resonance Energy Transfer
Dimerization
Protein-Tyrosine Kinases
Spectrum Analysis
Association reactions
Spectroscopy

Keywords

  • EGFR
  • FRET-FLIM
  • Ligand

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Predominance of activated EGFR higher-order oligomers on the cell surface. / Clayton, Andrew H A; Orchard, Suzanne G.; Nice, Edouard C.; Posner, Richard G; Burgess, Antony W.

In: Growth Factors, Vol. 26, No. 6, 2008, p. 316-324.

Research output: Contribution to journalArticle

Clayton, Andrew H A ; Orchard, Suzanne G. ; Nice, Edouard C. ; Posner, Richard G ; Burgess, Antony W. / Predominance of activated EGFR higher-order oligomers on the cell surface. In: Growth Factors. 2008 ; Vol. 26, No. 6. pp. 316-324.
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