Control of EGF receptor signalling: Lessons from fruitflies

The EGF receptor, and the related ErbB family of receptor tyrosine kinases, have been much implicated in human cancer. Hyperactive receptor signalling promotes deregulated growth control and the onset of malignancy, as well a s the disruption of developmental programmes. Very little, however, is know n about ErbB physiological regulation in humans. The fruitfly, Drosophila m elanogaster, has a single receptor homologous to the four ErbB receptors an d in this review we discuss how a genetic approach has led to significant i nsights into how the fly receptor is regulated. As signalling mechanisms ha ve been well conserved between flies and mammals, these results of experime nts in flies are relevant to the study of the human receptors in developmen t and disease. Two areas of recent progress are emphasised. First, a number of signal modulators have been identified, including three EGF receptor in hibitors, several of which have human homologues. Second, we describe how t he signalling molecules are integrated into regulatory networks that specif y the elaborate activation profiles needed in development - positive and ne gative feedback control of EGF receptor signalling emerges as a central the me. Although the study of the Drosophila EGF receptor has no direct clinica l application, the mechanistic insight it provides suggests new avenues of more applied research, including potential therapeutic targets.