TY - JOUR
T1 - Three loops of the common γ chain ectodomain required for the binding of interleukin-2 and interleukin-7
AU - Olosz, Ferenc
AU - Malek, Thomas R.
PY - 2000/9/29
Y1 - 2000/9/29
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M004976200
DO - 10.1074/jbc.M004976200
M3 - Article
C2 - 10887198
AN - SCOPUS:0034730722
VL - 275
SP - 30100
EP - 30105
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 39
ER -