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Revisiting a controversy: The effect of EGF on EGFR dimer stability.

Authors
  • Singh, Deo R1
  • King, Christopher2
  • Salotto, Matt3
  • Hristova, Kalina4
  • 1 Institute of NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America. , (United States)
  • 2 Institute of NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Program in Molecular Biophysics, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America. , (United States)
  • 3 Department of Materials Science and Engineering, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America. , (United States)
  • 4 Institute of NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Program in Molecular Biophysics, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Biochimica et biophysica acta. Biomembranes
Publication Date
Jan 01, 2020
Volume
1862
Issue
1
Pages
183015–183015
Identifiers
DOI: 10.1016/j.bbamem.2019.07.003
PMID: 31295474
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

EGFR is a receptor tyrosine kinase that plays a critical role in cell proliferation, differentiation, survival and migration. Its activating ligand, EGF, has long been believed to stabilize the EGFR dimer. Two research studies aimed at quantitative measurements of EGFR dimerization, however, have led to contradicting conclusions and have questioned this view. Given the controversy, here we sought to measure the dimerization of EGFR in the absence and in the presence of saturating EGF concentrations, and to tease out the effect of ligand on dimer stability, using a FRET-based quantitative method. Our measurements show that the dissociation constant is decreased ~150 times due to ligand binding, indicative of significant dimer stabilization. In addition, our measurements demonstrate that EGF binding induces a conformational change in the EGFR dimer. Copyright © 2019. Published by Elsevier B.V.

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