Argos (EGFR Inhibitor)

Argos is a secreted protein that is an inhibitor of the Epidermal Growth Factor Receptor (EGFR) pathway in "Drosophila melanogaster". 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 receptorref_N|1|a. Argos binds to the Epidermal growth factor domain of the "Drosophila" ligand Spitz and prevents its interaction with the Epidermal Growth Factor Receptor. Argos represents the first example of ligand sequestration as a mechanism of inhibition in the ErbB (EGFR) family.

Crystallographic studiesref_N|2|areveal 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 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 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 http://www.rcsb.org/pdb/explore/explore.do?structureId=3C9A]

References

ref_N|1|a Klein, Daryl E. et al. Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. "Nature 430, 1040–1044 (2004); doi:10.1038/nature02840

ref_N|2|a Klein, Daryl E. et al. Structural basis for EGFR ligand sequestration by Argos. "Nature (AOP May 25, 2008); doi:10.1038/nature06978