Abstract
Interleukin 7 (IL-7) is a pleiotropic cytokine which plays a role in both T and B cell function as well as in establishment and maintenance of immunological barriers in epithelial tissues. The heterodimeric IL-7 receptor (IL-7R) consists of the p76 IL-7Rα subunit and the p64 common gamma (γc) subunit. Ligand-binding induces signal transduction through tyrosine phosphorylation of the janus (Jak) and src-related kinases as well as by activation of phosphatidinositol-3 kinase (P13-kinase). In an effort to further define the requirements for ligand-receptor interactions and to subsequently develop candidate receptor binding antagonists with selective biological activities, we examined a series of IL-7 mutants in which the carboxy terminal hydrophobic residues were substituted with aliphatic amino acids. In this study we describe abrogation of IL-7 driven proliferation and attenuated phosphotyrosine signaling by IL-7(143) (Trp-Ala) and IL-7(143) (Trp-His) in IL-7R expressing T and B leukemia cells. Decreased phosphorylation of Jak3 kinase by IL-7W143A, IL-7W143P and IL-7W143H suggest that alterations in this region of the carboxyterminal region of IL-7 affects its interaction with the γc subunit of the IL-7R.
Original language | English (US) |
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Pages (from-to) | 17-22 |
Number of pages | 6 |
Journal | Cytokine |
Volume | 20 |
Issue number | 1 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- IL-7 signaling
- Lymphocytes
- γc-chain
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Biochemistry
- Hematology
- Molecular Biology