DOWN-REGULATION OF DROSOPHILA EGF-R MESSENGER-RNA LEVELS FOLLOWING HYPERACTIVATED RECEPTOR SIGNALING

Internalization of ligand-receptor complexes is a well-documented mech anism for limiting the duration and magnitude of a signaling event. In the case of the EGF-Receptor (EGF-R), exposure to EGF or TGF-alpha re sults in internalization of up to 95% of the surface receptor pool wit hin 5 minutes of exposure to ligand. In this report, we show that leve ls of Drosophila Egf-r mRNA are strongly down-regulated in epidermal c ells likely to have recently undergone high levels of EGF-R signaling. The cells in which Egf-r mRNA levels are down-regulated express the r homboid gene, which is thought to locally amplify EGF-R signaling. Wid espread Egf-r mRNA down-regulation can be induced by ubiquitous expres sion of rhomboid or by eliminating the Gap1 gene. These results sugges t that cells engaged in intense EGF-R/RAS signaling limit the duration of the signal through a combination of short-acting negative feedback mechanisms such as receptor internalization followed by a longer last ing reduction in receptor transcript levels. Control of Egf-r mRNA lev els by altering transcription or mRNA stability is a new tier of regul ation to be considered in analysis of EGF-R signaling during developme nt.