Proposed models for assembly of (A) GM-CSF–, IL-3–, and IL-5–induced receptor complexes and (B) preformed GM-CSF receptor complexes into activated receptors. In (A), GMRα, IL-3Rα, or IL-5Rα are in close proximity to (although not associated with) β_c on the cell surface. Ligand binding to the appropriate a chain induces α:β_c heterodimerization and a conformational change in a chain that allows its disulphide linkage to β_c . Modelling of β_c suggests that this bridging would only be possible if the unpaired cysteines in the α chain of receptor 1 formed a disulphide bridging with cysteine of β_c in receptor 2.18 The bringing together of two β_c with their associated JAK-2 molecules would then lead to receptor activation. In (B), it is postulated that the binding of IL-3 or IL-5 to their specific α chain and β_c triggers a conformational change in the α subunit analogous to model (A). However, in this case, a disulphide bridge can be formed between the free cysteine in the IL-3Rα or IL-5Rα and a cysteine in β_c that is already noncovalently associated with GMRα chain in a preformed complex. This interaction may be sufficient to bring together two β_c and two JAK-2 kinases leading to receptor activation. This model raises the possibility that some of the functions mediated by IL-3 and IL-5 are mediated inducibly through the activation of a preformed GMRα:β_c complex.