Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 31 August 2004
Vol. 2004, Issue 248, p. tw308
[DOI: 10.1126/stke.2482004tw308]

EDITORS' CHOICE

CELL BIOLOGY Argos Is a Spitz Sink

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]

Citation: Argos Is a Spitz Sink. Sci. STKE 2004, tw308 (2004).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882