Abstract
The residues located at the carboxyl terminus of helix D in interleukin-7 (IL-7) have previously been targeted as important for recruitment and binding to the γ chain component of the IL-7 receptor (IL-7R). In this study, Trp 143 of helix D was mutated to His, Phe, Tyr and Pro and these mutants, along with a W143A mutant previously described, were studied to determine the effects on activation of DNA synthesis and binding affinity to IL-7R positive 2E8 cells. The W143F and W143Y mutants were similar to wild type IL-7 in their binding properties and retained 85% and 74% of their activating properties, respectively. In contrast, the W143H mutant possessed a lower binding affinity and a corresponding decrease in activation, the W143A mutant possessed an over 100-fold decreased binding affinity and some residual activation activity and the W143P mutant possessed a greatly decreased binding affinity and did not activate. These results strongly suggest an aromatic residue is required at position 143 for IL-7R binding and subsequent signal transduction.
Original language | English (US) |
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Pages (from-to) | 227-233 |
Number of pages | 7 |
Journal | Cytokine |
Volume | 17 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- IL-7
- Mutational analysis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Biochemistry
- Hematology
- Molecular Biology