Epidermal growth factor-like ligands regulate dimer selection.

EGFR;receptors;ErbB;ErbB3;EGF;BTC

Jamie S. Rush

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: EGFR;    receptors;    ErbB;    ErbB3;    EGF;    BTC;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=4247&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

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.