Molecular structure of the IL‐3, GM‐CSF and IL‐5 receptors

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Abstract
Reconstitution of high‐affinity receptors using molecularly cloned receptor subunits has revealed that the high‐affinity receptors for interleukin 3 (IL‐3), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and IL‐5 are composed of two distinct subunits α and β. Both subunits are members of the cytokine receptor superfamily that have the common structural motif in their extracellular domains. The α subunits are cytokine‐specific, and each α subunit binds its specific ligand with low affinity. The human has a common β subunit that does not bind any cytokine by itself but forms high‐affinity receptors for GM‐CSF, IL‐3 and IL‐5 with the respective α subunit. Therefore, cross‐competition of binding between these cytokines occurs by competition for the common β subunit between different α subunits in the human. In contrast, the mouse has two distinct β subunits; one is specific for the IL‐3 receptor, and the other is equivalent to the human common β subunit. The β subunits are not only required for high‐affinity binding to ligands, but they are also essential for signal transduction. The high‐affinity receptors induce protein tyrosine phosphorylation and activate the ras protein. However, neither α nor β subunit has an intrinsic protein kinase, indicating that additional components are necessary for signal transduction.