Computational analysis of EGFR inhibition by Argos

Gregory T. Reeves, Rachel Kalifa, Daryl E. Klein, Mark A. Lemmon, Stanislav Y. Shvartsman

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)523-535
Number of pages13
JournalDevelopmental biology
Volume284
Issue number2
DOIs
StatePublished - Aug 15 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Argos
  • EGFR inhibition
  • Spitz

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