Argos (EGFR Inhibitor)
Encyclopedia
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 receptor. 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 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.
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
(EGFR) pathway in Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
. The name derives from the phenotype of mutant flies with eye defects and refers to Argus Panoptes
Argus Panoptes
In Greek mythology, Argus Panoptes or Argos, guardian of the heifer-nymph Io and son of Arestor, was a primordial giant whose epithet "Panoptes", "all-seeing", led to his being described with multiple, often one hundred, eyes. The epithet Panoptes was applied to the Titan of the Sun, Helios, and...
. The mechanism by which Argos attenuates the EGFR pathway is by sequestration of ligand and not by direct interaction with the receptor. Argos binds to the epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
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
ErbB
The ErbB protein family or epidermal growth factor receptor family is a family of four structurally related receptor tyrosine kinases. The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: Erythroblastic Leukemia Viral Oncogene...
(EGFR) family.
Crystallographic studies 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
Urokinase receptor
The Urokinase receptor, also known as uPA receptor or uPAR or CD87 , is multidomain glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol anchor...
. 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.