In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 38.3-38.3
Abstract:
Two isoforms of interleukin-15 (IL-15) are known, containing a long signal peptide (LSP) or a short signal peptide (SSP), respectively. The two forms are produced by alternatively spliced mRNAs. It has been proposed that SSP IL-15 remains exclusively intracellular and its function is not known. We show that, similar to LSP IL-15, SSP IL-15 is stabilized and secreted efficiently upon coexpression of IL-15 Receptor alpha (IL-15Ra). Co-injection of mice with SSP IL-15 and IL-15Ra expressing plasmids showed increased plasma levels of bioactive IL-15 and mobilization and expansion of NK and T cells. Therefore, SSP IL-15 is secreted and bioactive when produced as a heterodimer with IL-15Ra in the same cell, though its apparent stability is lower compared to LSP IL-15, due to different intracellular processing. When both LSP IL-15 and SSP IL-15 are produced in the same cell they compete for the binding to IL-15Ra, and result in lower levels of bioactive IL-15. Therefore, co-expressed SSP IL-15 acts as competitive inhibitor of LSP IL-15. This suggests that usage of alternative splicing is an additional level of control of IL-15 activity. Expression of both SSP and LSP forms of IL-15 appears to be conserved in many mammals, suggesting that SSP may be important for expressing a form of IL-15 with lower magnitude and duration of biological effects. These results support and expand our conclusions (Bergamaschi, J Biol Chem. 2008; 283:4189) that IL-15Ra needs to be co-expressed in the same cell with IL-15 for biological activity, and that IL-15Ra should be considered a part of the heterodimeric IL-15 cytokine, rather than part of the receptor.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.182.Supp.38.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
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