Functional characterization of the human interleukin-15 receptor α chain and close linkage of IL15RA and IL2RA genes

Dirk M. Anderson, Satoru Kumaki, Minoo Ahdieh, Jeanette Bertles, Mark Tometsko, Aaron Loomis, Judith Giri, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Virginia Valentine, David N. Shapiro, Stephan W. Morris, Linda S. Park, David Cosman

Research output: Contribution to journalArticle

313 Scopus citations

Abstract

Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but distinct biological effects. Their receptors share two subunits (the IL-2Rβ and -γ chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific α subunit for high affinity IL-2 binding. Recently, a murine IL-15-specific α subunit was identified, cloned, and shown to be structurally related to IL-2Rα. However, the murine IL- 15Rα alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2Rα and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15Rα variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL- 15Rα, like that of IL-2Rα, is dispensable for mitogenic signaling, suggesting that the primary role of the α chains is to confer high affinity binding. At high concentrations, IL-15, like IL-2, is able to signal through a complex of IL-2Rβ and -γ in the absence of the α subunit. Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization and are closely linked in both human and murine genomes. However, the distribution of expression of the IL-15Rα is much wider than that of the IL-2Rα, suggesting a broader range of cellular targets for IL-15.

Original languageEnglish (US)
Pages (from-to)29862-29869
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number50
DOIs
StatePublished - Dec 15 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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