Receptor biology

Argos Und Der Spitz

Science's STKE  14 Mar 2000:
Vol. 2000, Issue 23, pp. tw8
DOI: 10.1126/stke.2000.23.tw8

The proteins Vein, Gurken, and Spitz (Spi) each activate the Drosophila epidermal growth factor receptor (DER). The Argos (Aos) protein blocks DER signaling; however, the mechanism of inhibition is unclear. Jin et al. used DER-expressing cells and a chimera of the extracellular domain of DER fused to an antibody fragment (Fc) and determined that Aos binds the extracellular domain of DER. Preincubation of DER-expressing cells with Aos blocked Spi binding to DER. The authors used cross-linking studies to show that Spi induced the dimerization of endogenous DER, but that Aos could inhibit this dimerization. Similarly, Spi-independent DER dimerization and activation, caused by overexpression of DER, was blocked by Aos, indicating that Aos can disrupt DER dimer formation. Thus, Aos can inhibit signaling by blocking ligand binding and by preventing receptor dimerization.

Jin, M.-H., Sawamoto, K., Ito, M., and Okano, H. (2000) The interaction between the Drosophila secreted protein Argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted Spitz to the receptor. Mol. Cell. Biol. 20: 2098-2107. [Abstract] [Full Text]