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

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-7Ralpha subunit and the p64 common gamma (gammac) 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 gammac subunit of the IL-7R.

• Authors: Güllü Görgün, Johanna van der Spek, Larry Cosenza, Adnan Menevse, Francine Foss
• Journal: Cytokine (Cytokine) Vol. 20 Issue 1 Pg. 17-22 (Oct 07 2002) ISSN: 1043-4666 [Print] England
• PMID: 12441142 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-7

Topics

• Blotting, Western
• Cell Division
• Humans
• Interleukin-7 (chemistry, physiology)
• Precipitin Tests