Signalling through the Drosophila EGF receptor (DER), which is involved in several developmental processes, is controlled by activating and inhibiting ligands. On p. 4483, Ghiglione et al. examine how one inhibitor, Kekkon 1 (Kek1), achieves the negative feedback control of DER that occurs during Drosophila oogenesis and imaginal disc development. Their structure-function analyses show that the extracellular, leucine-rich repeat domains of Kek1 are needed for the in vivo association of Kek1 and DER as a heterodimer. Their findings also show that, in mammalian cell-based assays, the interaction of Kek1 with mammalian ErbB growth factor receptor tyrosine kinases blocks activating ligands from binding these receptors, as well as blocking their autophosphorylation and subsequent signal transduction. Given the overexpression of some of these receptors in human tumours, Ghiglione et al. suggest that Kek1 or its unknown mammalian homologues might have clinical utility as anti-tumour agents.
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