Matches in SemOpenAlex for { <https://semopenalex.org/work/W2898830069> ?p ?o ?g. }
- W2898830069 abstract "Abstract The epidermal growth factor receptor (EGFR) is a membrane protein that regulates cell proliferation, differentiation and survival, and is a drug target for cancer therapy. Ligand-induced activation of the EGFR kinase is generally regarded to require ligand-bound-dimers, while phosphorylation and downstream signalling is modulated by higher-order oligomers. Recent work has unveiled changes in EGFR dynamics from ligand-induced dimerization in membranes extracted from cells, however less is known about the changes in EGFR dynamics that accompany the ligand-induced dimer to tetramer transition in a live cell environment. In the present report, we determine the dynamics of a c-terminal GFP tag attached to EGFR in the unliganded dimer and in the liganded tetramer by means of dynamic depolarization microscopy. We made use of a novel analysis method, the single-frequency polarized phasor ellipse approach, to extract two correlation times on the subnanosecond and super-nanosecond timescales, respectively. EGF binding to the EGFR-GFP dimer lengthened the sub-nanosecond correlation time (from 0.1ns to 1.3ns), and shortened the supernanosecond correlation time (from 210ns to 56ns) of the c-terminal GFP probe. The sub-nanosecond depolarization processes were assigned to electronic energy migration between proximal GFPs in the EGFR dimer or oligomer, while the super-nanosecond correlation times were assigned to nanosecond fluctuations of the GFP probe in the EGFR complex. Accordingly, these results show that ligand binding to the extracellular domain increased the average separation between the c-terminal tags and increased their rotational mobility. We propose that the dynamics are linked to an inhibitory function of the c-terminal tail in the un-liganded dimer and to the requirement of facile stochastic switching between kinase activation and cytoplasmic adaptor/effector binding in the active tetramer." @default.
- W2898830069 created "2018-11-09" @default.
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- W2898830069 date "2018-10-31" @default.
- W2898830069 modified "2023-09-23" @default.
- W2898830069 title "In-Cell Structural Dynamics of an EGF Receptor during Ligand-induced Dimer-Oligomer Transition" @default.
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- W2898830069 doi "https://doi.org/10.1101/458265" @default.
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