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

Gullu Gorgun, Johanna Van Der Spek, Larry Cosenza, Adnan Menevse, Francine Foss

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 - 2002
Externally publishedYes

Fingerprint

Interleukin-7
Interleukin-7 Receptors
Bioactivity
Phosphotransferases
Phosphorylation
tryptophyl-histidine
B-Cell Leukemia
Ligands
T-Cell Leukemia
Signal transduction
Phosphotyrosine
src-Family Kinases
Tyrosine
Signal Transduction
B-Lymphocytes
Fatty Acids
Epithelium
Chemical activation
Cells
Maintenance

Keywords

  • γc-chain
  • IL-7 signaling
  • Lymphocytes

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Gorgun, 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

Altered biological activity associated with C-terminal modifications of IL-7. / Gorgun, Gullu; Van Der Spek, Johanna; Cosenza, Larry; Menevse, Adnan; Foss, Francine.

In: Cytokine, Vol. 20, No. 1, 2002, p. 17-22.

Research output: Contribution to journalArticle

Gorgun, G, Van Der Spek, J, Cosenza, L, Menevse, A & Foss, F 2002, 'Altered biological activity associated with C-terminal modifications of IL-7', Cytokine, vol. 20, no. 1, pp. 17-22. https://doi.org/10.1006/cyto.2002.1974
Gorgun, Gullu ; Van Der Spek, Johanna ; Cosenza, Larry ; Menevse, Adnan ; Foss, Francine. / Altered biological activity associated with C-terminal modifications of IL-7. In: Cytokine. 2002 ; Vol. 20, No. 1. pp. 17-22.
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