Comparison of EGFR Dimer Stabilities in the Presence and Absence of the Ligand EGF

Abstract

EGFR is a member of the ErbB family of receptors. EGFR consists of a glycosylated extracellular domain, a single pass transmembrane segment, and an intracellular domain with kinase activity. Mutations or increased expression of this receptor have been linked to human cancers. EGF is a ligand that binds and activates EGFR. It is generally accepted that EGF binding increases the stability of EGFR dimers. However, the magnitude of this stabilizing effect has not been quantified yet. Here, we used spectral FRET, combined with two photon microscopy, to study the dimerization of EGFR in plasma membranes. We observed significant stabilization of the EGFR dimer in the presence of the EGF ligand. These data allowed us to quantify the increase in EGFR dimer stability upon EGF binding.