Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes - PubMed (original) (raw)
Comparative Study
. 1995 Dec 15;270(50):29862-9.
doi: 10.1074/jbc.270.50.29862.
Affiliations
- PMID: 8530383
- DOI: 10.1074/jbc.270.50.29862
Free article
Comparative Study
Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes
D M Anderson et al. J Biol Chem. 1995.
Free article
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-2R beta and -gamma chains) that are essential for signal transduction. The IL-2 receptor requires an additional IL-2-specific alpha subunit for high affinity IL-2 binding. Recently, a murine IL-15-specific alpha subunit was identified, cloned, and shown to be structurally related to IL-2R alpha. However, the murine IL-15R alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL-2R alpha and IL-2. We now extend these studies into the human system with the isolation of three differentially spliced human IL-15R alpha variants that are all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling, suggesting that the primary role of the alpha chains is to confer high affinity binding. At high concentrations, IL-15, like IL-2, is able to signal through a complex of IL-2R beta and -gamma in the absence of the alpha 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-15R alpha is much wider than that of the IL-2R alpha, suggesting a broader range of cellular targets for IL-15.
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