Computational analysis of EGFR inhibition by Argos. Author Gregory Reeves, Rachel Kalifa, Daryl Klein, Mark Lemmon, Stanislav Shvartsman Publication Year 2005 Type Journal Article Abstract Argos, a secreted inhibitor of the Drosophila epidermal growth factor receptor, and the only known secreted receptor tyrosine kinase inhibitor, acts by sequestering the EGFR ligand Spitz. We use computational modeling to show that this biochemically-determined mechanism of Argos action can explain available genetic data for EGFR/Spitz/Argos interactions in vivo. We find that efficient Spitz sequestration by Argos is key for explaining the existing data and for providing a robust feedback loop that modulates the Spitz gradient in embryonic ventral ectoderm patterning. Computational analysis of the EGFR/Spitz/Argos module in the ventral ectoderm shows that Argos need not be long-ranged to account for genetic data, and can actually have very short range. In our models, Argos with long or short length scale functions to limit the range and action of secreted Spitz. Thus, the spatial range of Argos does not have to be tightly regulated or may act at different ranges in distinct developmental contexts. Keywords Animals, Drosophila, Drosophila Proteins, Mutation, In Situ Hybridization, Models, Biological, Genes, Insect, Membrane Proteins, Computational Biology, RNA, Messenger, Body Patterning, DNA-Binding Proteins, Gene Dosage, Ectoderm, Nuclear Proteins, Basic Helix-Loop-Helix Transcription Factors, Receptor, Epidermal Growth Factor, Feedback, Physiological, Kinetics, Insect Proteins, Enzyme Induction, Eye Proteins, Epidermal Growth Factor, Nerve Tissue Proteins Journal Dev Biol Volume 284 Issue 2 Pages 523-35 Date Published 08/2005 Alternate Journal Dev. Biol. Google ScholarBibTeXEndNote X3 XML