Down-regulation of Drosophila Egf-r mRNA levels following hyperactivated receptor signaling.
Internalization of ligand-receptor complexes is a well-documented mechanism 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 results in internalization of up to 95% of the surface receptor pool within 5 minutes of exposure to ligand. In this report, we show that levels of Drosophila Egf-r mRNA are strongly down-regulated in epidermal cells likely to have recently undergone high levels of EGF-R signaling. The cells in which Egf-r mRNA levels are down-regulated express the rhomboid gene, which is thought to locally amplify EGF-R signaling. Widespread Egf-r mRNA down-regulation can be induced by ubiquitous expression of rhomboid or by eliminating the Gap1 gene. These results suggest 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 lasting reduction in receptor transcript levels. Control of Egf-r mRNA levels by altering transcription or mRNA stability is a new tier of regulation to be considered in analysis of EGF-R signaling during development.
Department of Biology, University of California San Diego, La Jolla 92093.
M A
MA
Sturtevant
J W
JW
O'Neill
E
E
Bier
D000818:Animals; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D066246:ErbB Receptors / Q000235:genetics*; D005246:Feedback; D017403:In Situ Hybridization; D007301:Insect Hormones / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D011494:Protein Kinases; D012333:RNA, Messenger / Q000032:analysis; D018010:Receptors, Invertebrate Peptide / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; D012333:RNA, Messenger; D018010:Receptors, Invertebrate Peptide; C081481:Rho protein, Drosophila; C472498:Stet protein, Drosophila; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors