Regulation of EGF receptor signaling in the fruitfly D. melanogaster and the nematode C. elegans

Mammals contain four members (HER1/EGFR, HER2/Neu, HER3, and HER4) of the epidermal growth factor receptor (EGFR) family, which transduce extracellular signals by EGF family peptide growth factors. Upon binding of ligand with receptor, dimerization and auto-phosphorylation of the receptor results in a cascade of events which transmit signal from the cell surface to the nucleus. Amplification and/or uncontrolled signaling of these receptors is associated with many cancers. 10 to 34% of human breast cancers are associated with amplification or overexpression of the HER2/neu oncogene, an EGFR homolog [1]. Signaling from the EGFR plays a critical role in the development of many organisms including the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, each of which contain a single EGFR homolog. The powerful genetic techniques offered by these organisms has allowed new components of the EGFR signal transduction pathway to be identified as well as lending insight into the basis of tissue specificity of signaling.