The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis

We have identified the Drosophila transmembrane molecule kekkon 1 (kek1) as an inhibitor of the epidermal growth factor receptor (EGFR) and demonstrat e that it acts in a negative feedback loop to modulate the activity of the EGFR tyrosine kinase. During oogenesis, kek1 is expressed in response to th e Gurken/EGFR signaling pathway, and loss of kek1 activity is associated wi th an increase in EGFR signaling. Consistent with our loss-of-function stud ies, we demonstrate that ectopic overexpression of kek1 mimics a loss of EG FR activity. We show that the extracellular and transmembrane domains of Ke k1 can inhibit and physically associate with the EGFR, suggesting potential models for this inhibitory mechanism.