Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 38, Pages 13353-13362Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA120.012852
Keywords
epidermal growth factor receptor; receptor tyrosine kinase; signal transduction; membrane protein; oligomerization; fluorescence resonance energy transfer; FRET; EGFR
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Funding
- National Institutes of Health [5R01GM099321-17]
- Cancer Prevention Research Institute of Texas (CPRIT) Grant [RR160023]
- National Science Foundation (NSF) [MCB-1712740]
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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.
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