期刊
DEVELOPMENTAL BIOLOGY
卷 284, 期 2, 页码 523-535出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2005.05.013
关键词
EGFR inhibition; Argos; Spitz
资金
- NCI NIH HHS [BC030019, R01 CA125432-04, R01 CA125432, R01-CA079992] Funding Source: Medline
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. (c) 2005 Elsevier Inc. All rights reserved.
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