GM-CSF Ra - Fc
A DNA sequence encoding the signal peptide and extracellular domain of human GM-CSF Ralpha (aa 1-320) was fused to the Fc region of human IgG1 (aa 90-330). The chimeric protein was expressed in modified human 293 cells. Human GM-CSF receptor is composed of an alpha and a beta subunit. The alpha subunit (GM-CSF R alpha) binds to GM-CSF, and when assoicated with the beta subunit (CRC beta, Common Receptor Chain beta, GM-CSF R beta) it forms a high affinity receptor. GM-CSF R alpha has 11 potential N-glycosylation sites all located in the extracellular domain. N-glycosylation of the alpha subunit is essential for GM-CSF binding and signalling [Ding et al. (1995) J Biol Chem 270:24580-24584]. Symansis GM-CSF R alpha is produced as an ECD-Fc fusion protein with the aim of enhancing its activity. ECD-Fc fusion proteins have an advantage over soluble receptors because many receptors are only functional in dimeric form. Fusion to the Fc domain of IgG1 induces dimerization due to the ability of the Fc domain to form disulfide bonds. The resulting dimeric receptor ECD-Fc mimics the activated form of the receptor and possess enhanced affinity for its cognate ligand relative to its monomeric form. For a recent review please see Baj et al. (2000) Eur J Gynaecol Oncol 21:305-308.