GM-CSF binding to its receptor induces oligomerisation of the common beta-subunit

The stoichiometry of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor complex is still unresolved. We have utilised a sensitive, functional assay for receptor homodimerisation to show that GM-CSF induces dimerisation of the common signalling subunit, hβ_c. We generated a chimeric cytokine receptor in which the extracellular and transmembrane domains of hilt are fused to the cytoplasmic domain of erythropoietin receptor (EPO-R). Given that to induce EPO-R activation and mitogenic signalling there is a requirement for formation of a specific homodimeric complex, we reasoned that the cytoplasmic domain of EPO-R could be utilised as a highly sensitive reporter for functional homodimer formation. We show that, in the presence of a cytoplasmically truncated GM-CSF α-subunit, the hβc-EPO receptor chimera transduces a mitogenic signal in BaF-B03 in response to GM-CSF. This is consistent with formation of a hβ_c homodimer following GM-CSF binding and implies that ligand stimulation induces formation of a higher order complex that contains the hβ_c homodimer.