Altered biological activity associated with C-terminal modifications of IL-7

Güllü Görgün, Johanna Van Der Spek, Larry Cosenza, Adnan Menevse, Francine Foss

Research output: Contribution to journalArticle

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)17-22
Number of pages6
JournalCytokine
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • IL-7 signaling
  • Lymphocytes
  • γc-chain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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  • Cite this

    Görgün, G., Van Der Spek, J., Cosenza, L., Menevse, A., & Foss, F. (2002). Altered biological activity associated with C-terminal modifications of IL-7. Cytokine, 20(1), 17-22. https://doi.org/10.1006/cyto.2002.1974