Schematic representation of possible GM-CSF, IL-3, and IL-5 receptor complexes. (A) The receptor α and β_c interaction in the absence of ligand. The cartoon illustrates that the N-terminus of the α chain has approximately 90° angle flexibility from the CRM. In the case of the IL-3R24 and probably also of the IL-5R, the α and β_c subunits are not associated either covalently (disulfide linked) or noncovalently. In the case of the GM-CSFR, there is no disulfide linkage but there is probably a noncovalent association through domain 2 of the GMRα CRM and domain 4 of β_c . (B) In a dynamic and probably reversible manner, β_c can homodimerize by disulfide linkage. However, this is a nonproductive interaction because no tyrosine phosphorylation of β_c is seen (see also Fig 3).63 (C) The binding of ligand to these receptors may then give rise to a trimer with a ligand:α:β_c stoichiometry of 1:1:1. However, the 180° angle required for the α subunit to link up with β_c makes this possibility unlikely. Instead, (D) illustrates a more likely ligand:α:β_c stoichiometry of 2:2:2 where the α subunit of receptor 1 forms a disulfide bond with β_c of receptor 2 and the α subunit of receptor 2 forms a disulfide bond with β_c of receptor 1. The free cysteines in the α and β_c subunits are illustrated.