Argos (EGFR Inhibitor)

Argos is a secreted protein that is an inhibitor of the epidermal growth factor receptor (EGFR) pathway in Drosophila melanogaster.[1][2] The name derives from the phenotype of mutant flies with eye defects and refers to Argus Panoptes. The mechanism by which Argos attenuates the EGFR pathway is by sequestration of ligand and not by direct interaction with the receptor.[3] Argos binds to the epidermal growth factor domain of the Drosophila ligand Spitz and prevents its interaction with the EGFR. Argos represents the first example of ligand sequestration as a mechanism of inhibition in the ErbB (EGFR) family.

Crystallographic studies[4] reveal that Argos does not contain an EGF domain as originally expected. Rather, Argos is composed of 3 separate domains that have homology to one another, termed the Argos domain. The Argos domain has features in common with the three finger toxin fold that is found in a number of proteins including TGF beta receptors and the urokinase (uPA) receptor. Thus, the EGF decoy receptor Argos shares structural homology to receptors from the TGF beta and uPA families. A yet to be discovered human Argos may be found among related structures.

The structure of Argos in complex with an EGFR ligand can be found at the Protein Data Bank under code 3C9A.

See also

References

  1. ↑ M. Freeman, C. Klambt, C. S. Goodman, G. M. Rubin, Cell 69, 963 (1992)
  2. ↑ R. Schweitzer, R. Howes, R. Smith, B.-Z. Shilo, M. Freeman, Nature 376, 699 (1995)
  3. ↑ Klein, D. E.; Nappi, V. M.; Reeves, G. T.; Shvartsman, S. Y.; Lemmon, M. A. (2004). "Argos inhibits epidermal growth factor receptor signalling by ligand sequestration". Nature 430 (7003): 1040–4. Bibcode:2004Natur.430.1040K. doi:10.1038/nature02840. PMID 15329724.
  4. ↑ Klein, D. E.; Stayrook, S. E.; Shi, F.; Narayan, K.; Lemmon, M. A. (2008). "Structural basis for EGFR ligand sequestration by Argos". Nature 453 (7199): 1271–5. Bibcode:2008Natur.453.1271K. doi:10.1038/nature06978. PMC 2526102. PMID 18500331.


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