Interleukin-2 (IL-2)-mediated induction of the IL-2 receptor chain gene: Critical role of two functionally redundant tyrosine residues in the IL-2 receptor β chain cytoplasmic domain and suggestion that these residues mediate more than STAT5 activation

Dana P. Ascherman, Thi Sau Migone, Michael C. Friedmann, Warren J. Leonard

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The interleukin-2 receptor α chain (IL-2Rα) is potently induced by antigens, mitogens, and certain cytokines that include IL-2 itself. This induction leads to the formation of high affinity IL-2 receptors when IL- 2Rα is co-expressed with the β (IL-2Rβ) and γ (γ(c)) chains of this receptor. We investigated the signaling pathways mediating IL-2-induced IL- 2Rα mRNA expression using 32D myeloid progenitor cells stably transfected with either wild type IL-2Rβ or mutants of IL-2Rβ containing tyrosine to phenylalanine substitutions. Of the six cytoplasmic tyrosines in IL-2Rβ, we have found that only the two tyrosines that mediate Stat5 activation (Tyr- 392 and Tyr-510) contribute to IL-2-induced IL-2Rα gene expression and that either tyrosine alone is sufficient for this process. Interestingly, the IL- 7 receptor contains a tyrosine (Tyr-429)-based sequence resembling the motifs encompassing Tyr-392 and Tyr-510 of IL-2Rβ. Further paralleling the IL-2 system, IL-7 could activate Stats and drive expression of IL-2Rα mRNA in 32D cells transfected with the human IL-7R. However, IL-3 could not induce IL- 2Rα mRNA in 32D cells, despite its ability to activate Stats via the endogenous IL-3 receptor. Moreover, the combination of IL-3 and IL-2 could not 'rescue' IL-2Rα mRNA expression in cells containing an IL-2β mutant with phenylalanine substitutions at Tyr-392 and Tyr-510. These data suggest that Tyr-392 and Tyr-510 couple to an additional signaling pathway beyond STAT protein activation in IL-2-mediated induction of the IL-2Rα gone.

Original languageEnglish (US)
Pages (from-to)8704-8709
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number13
DOIs
StatePublished - Mar 28 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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