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J Biol Chem. 1997 Mar 28;272(13):8704-9.

Interleukin-2 (IL-2)-mediated induction of the IL-2 receptor alpha chain gene. Critical role of two functionally redundant tyrosine residues in the IL-2 receptor beta chain cytoplasmic domain and suggestion that these residues mediate more than Stat5 activation.

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  • 1Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.

Abstract

The interleukin-2 receptor alpha chain (IL-2Ralpha) 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-2Ralpha is co-expressed with the beta (IL-2Rbeta) and gamma (gammac) chains of this receptor. We investigated the signaling pathways mediating IL-2-induced IL-2Ralpha mRNA expression using 32D myeloid progenitor cells stably transfected with either wild type IL-2Rbeta or mutants of IL-2Rbeta containing tyrosine to phenylalanine substitutions. Of the six cytoplasmic tyrosines in IL-2Rbeta, we have found that only the two tyrosines that mediate Stat5 activation (Tyr-392 and Tyr-510) contribute to IL-2-induced IL-2Ralpha 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-2Rbeta. Further paralleling the IL-2 system, IL-7 could activate Stat5 and drive expression of IL-2Ralpha mRNA in 32D cells transfected with the human IL-7R. However, IL-3 could not induce IL-2Ralpha mRNA in 32D cells, despite its ability to activate Stat5 via the endogenous IL-3 receptor. Moreover, the combination of IL-3 and IL-2 could not "rescue" IL-2Ralpha mRNA expression in cells containing an IL-2Rbeta 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-2Ralpha gene.

PMID:
9079703
[PubMed - indexed for MEDLINE]
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