MOLECULAR-STRUCTURE OF THE IL-3, GM-CSF AND IL-5 RECEPTORS

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-alpha and beta. Both subunits are members of the cytokine receptor superfamily that have the common structural motif in their extracellular domains. The alpha-subunits are cytokine-specific. and each alpha-subunit binds its specific ligand with low affinity. The human has a common beta-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 alpha-subunit. Therefore, cross-competition of binding between these cytokines occurs by competition for the common beta-subunit between different alpha-subunits in the human. In contrast, the mouse has two distinct beta-subunits, one is specific for the lL-3 receptor, and the other is equivalent to the human common beta-subunit. The beta-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 alpha nor beta-subunit has an intrinsic protein kinase, indicating that additional components are necessary for signal transduction.