Regulation of ErbB Receptor Tyrosine Kinase Activities in Breast Cancer by the Kek Proteins

摘要

We have found that the Drosophila transmembrane molecule kekkon-1 (kek1) acts in a negative feed back loop to modulate the activity of the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase. kek1 is expressed in response to activation of the Gurken/EGFR signaling pathway during oogenesis. While loss of kek1 activity is associated with a phenotype reminiscent of increased Grk/EGFR signaling, ectopic overexpression of kek1 mimics the complete loss of EGFR activity. We found that the extracellular domain of Kek1 physically associates with the EGFR providing the basis for this inhibitory mechanism. Interestingly, we found that Kek1 is also a potent inhibitor of the EGFR in mammalian cells.