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Activation and Inhibition of the EGF Receptor
Author(s) -
Lemmon Mark Andrew
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a46-b
Subject(s) - epidermal growth factor receptor , epidermal growth factor , receptor tyrosine kinase , microbiology and biotechnology , erbb , extracellular , signal transduction , receptor , biology , tyrosine kinase , cell surface receptor , cell signaling , erbb4 , chemistry , biochemistry
The epidermal growth factor (EGF) receptor is the prototype of the ErbB (Her) family receptor tyrosine kinases (RTKs), which regulate cell growth and differentiation and are implicated in many human cancers. EGF activates its receptor (EGFR) by inducing dimerization of the 621 amino acid EGFR extracellular region. I will describe our current mechanistic view of EGF‐induced dimerization and activation of EGFR based on crystallographic and other studies. I will also describe how studies of the EGFR orthologs from D. melanogaster and C. elegans help in translating lessons learned with isolated extracellular domains to the cell surface. Invertebrates have evolved several mechanisms to inhibit signaling by their EGFR orthologs that have not been described in mammals. The secreted molecule Argos acts as a ‘ligand sink’ that effectively neutralizes EGFR‐activating ligands. Kekkon‐1 is a membrane protein that interacts directly with (and inhibits) EGFR. I will discuss our current studies of inhibition of EGFR signaling through these mechanisms, which offer lessons for the design of novel EGFR‐targeted therapeutic strategies in humans.