The receptor for granulocyte/macrophage colony‐stimulating factor (GM‐CSF) consists of a ligand‐specific low‐affinity binding chain (GM‐CSFRα) and a second chain that is required for high‐affinity binding and signal transduction. This second chain is shared by the ligand‐specific α‐chains for the interleukin 3 (IL‐3) and IL‐5 receptors and is therefore called β common (β_c). In mice but not humans the IL‐3 receptor can also use a closely related but IL‐3‐specific β‐chain (β_IL‐3). In order to define the contributions of each chain to receptor signalling we generated mice in which either β_c or β_IL‐3 expression was deleted. β_IL‐3 null mice were phenotypically normal but displayed a decreased responsiveness to IL‐3 in vitro. β_c null mice, on the other hand, were unresponsive to GM‐CSF or IL‐5 but still responded to IL‐3. These data demonstrated that GM‐CSF and IL‐5 receptors can use only one β‐chain for signalling (β_c) while IL‐3 can effectively use either β‐chain. The hierarchical basis of receptor transmodulation was shown to result from this differential usage of β‐chains. To define the regions required for different types of cell signalling, we constructed human β_c mutants with successive cytoplasmic truncations. By the use of appropriate biological read‐out systems we found that the cytoplasmic region of the receptor has a modular design with distinct domains required for cell proliferation, cell survival, differentiation and growth suppression. Appropriate targeting of these domains and the signalling pathways they initiate may provide highly specific cell therapies in the future.