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 IL-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.
Miyajima
A
A
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304.
D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000737:chemistry* / Q000378:metabolism; D015848:Interleukin-5; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5
D007377:Interleukin-3; D015848:Interleukin-5; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor