The common γ chain (γc), a subunit of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors, contributes to both cytokine binding and subsequent signal transduction. Using a model-based site-directed mutagenesis strategy, we have identified residues of the mouse γc extracellular domain that are required for normal γc-dependent enhancement of IL-2 and IL-7 binding. One of these sites, Tyr-103, is homologous to key ligand-interacting residues in the growth hormone and erythropoietin receptors, whereas Cys-161, Cys-210, and Gly-211 may function indirectly by maintaining the functional conformation of γc via formation of an intramolecular disulfide bond. These two cysteines are also required for the integrity of a putative epitope recognized by TUGm2, an antagonistic monoclonal antibody that blocks γc-dependent cytokine binding and bioactivity. These results are consistent with the involvement of three predicted loops in γc that contribute to the binding of both IL-2 and IL-7. Mutations in these loops have also been noted in the γc gene of patients with X-linked severe combined immunodeficiency.
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - Sep 29 2000|
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