Date on Master's Thesis/Doctoral Dissertation
12-2018
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, MS
Committee Chair
Ceresa, Brian P.
Committee Co-Chair (if applicable)
Hood, Joshua L.
Committee Member
Hood, Joshua L.
Committee Member
Bates, Paula J.
Author's Keywords
EGFR; receptors; ErbB; ErbB3; EGF; BTC
Abstract
There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than EGF, without noticeable differences in effector signaling. Thus, we demonstrate that despite both ligands binding to the EGFR, BTC biases the EGFR to dimerize with ErbB3 and regulates the biological response through trafficking and unknown effectors.
Recommended Citation
Rush, Jamie S., "Epidermal growth factor-like ligands regulate dimer selection." (2018). Electronic Theses and Dissertations. Paper 3122.
https://doi.org/10.18297/etd/3122
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