Cell Biology

Argos Is a Spitz Sink

Science's STKE  31 Aug 2004:
Vol. 2004, Issue 248, pp. tw308
DOI: 10.1126/stke.2482004tw308

Argos, a secreted protein, was identified as an inhibitor of Drosophila epidermal growth factor (EGF) receptor (DER) signaling. Klein et al. report an unexpected mechanism of action for Argos. In surface plasmon resonance and ultracentrifugation experiments, Argos interacted not with the receptor, but with the ligand Spitz. When added to the medium of cultured cells transfected to express the DER, Argos inhibited DER tyrosine phosphorylation stimulated in response to Spitz. DER activation was detected if Spitz was added to the cells prior to the addition of Argos. However, preaddition of Argos or simultaneous addition of Argos and Spitz prevented DER activation. These results all are consistent with Argos serving as a ligand sink, preventing Spitz from binding and activating the receptor. Similar to the bone morphogenetic protein (BMP) antagonist Noggin, which is also a ligand sink inhibitor, Argos appeared to associate with heparan sulphate proteoglycans on the cell surface. The EGF ligand (Spitz) is now one of several ligands whose activity is limited through the actions of a sequestering antagonist (Argos).

D. E. Klein, V. M. Nappi, G. T. Reeves, S. Y. Shvartsman, M. A. Lemmon, Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. Nature 430, 1040-1044 (2004). [Online Journal]