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Isoforms1
* Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany;
Department of Urology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany; and
Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany
Mast cells previously have been reported to be regulated by IL-15 and to express a distinct IL-15R, termed IL-15RX. To further examine IL-15 binding and signaling in mast cells, we have studied the nature of the IL-15R and some of its biological activities in these cells. In this study, we report the existence of three novel isoforms of the IL-15R
chain in murine bone marrow-derived mast cells as a result of an alternative exon-splicing mechanism within the IL-15R gene. These correspond to new mRNA transcripts lacking exon 4; exons 3 and 4; or exons 3, 4, and 5 (IL-15R
4, IL-15R3,4, IL-15R3,4,5). After transient transfection in COS-7 cells, all IL-15R isoforms associate with the Golgi apparatus, the endoplasmic reticulum, the perinuclear space, and the cell membrane. Analysis of glycosylation pattern demonstrates the usage of a single N-glycosylation site, while no O-glycosylation is observed. Importantly, IL-15 binds with high affinity to, and promotes the survival of, murine BA/F3 cells stably transfected with the IL-15R isoforms. Furthermore, we report that signaling mediated by IL-15 binding to the newly identified IL-15R isoforms involves the phosphorylation of STAT3, STAT5, STAT6, Janus kinase 2, and Syk kinase. Taken together, our data indicate that murine mast cells express novel, fully functional IL-15R isoforms, which can explain the selective regulatory effects of IL-15 on these cells.
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