Soluble Interleukin (IL)-15Rα Is Generated by Alternative Splicing or Proteolytic Cleavage and Forms Functional Complexes with IL-15
| Autor: | Erwin Hans Duitman, Silvia Bulfone-Paus, Vadim Budagian, Hans Krause, Norbert Reiling, René Rückert, Zane Orinska, Elena Bulanova |
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| Rok vydání: | 2007 |
| Předmět: |
Sushi domain
Proteolysis ADAM17 Protein Biology Biochemistry Interferon-gamma Mice Chlorocebus aethiops medicine Animals Humans Protein Isoforms Receptor Molecular Biology Cell Proliferation Interleukin-15 Mice Knockout medicine.diagnostic_test Receptors Interleukin-15 Alternative splicing Interleukin Cell Biology Cell biology Killer Cells Natural ADAM Proteins Alternative Splicing Ectodomain Interleukin 15 Multiprotein Complexes COS Cells Immunology Additions and Corrections Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 282:13167-13179 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m610036200 |
| Popis: | Interleukin 15 (IL-15) is a pleiotropic cytokine that is hardly detectable in biological fluids. Here, we show that IL-15 forms functional heterocomplexes with soluble high affinity IL-15 receptor alpha (IL-15Ralpha) chain in mouse serum and cell-conditioned medium, which prevents IL-15 detection by ELISA. We also demonstrate that two soluble IL-15Ralpha (sIL-15Ralpha) sushi domain isoforms are generated through a novel alternative splicing mechanism within the IL-15Ralpha gene. These isoforms potentiate IL-15 action by promoting the IL-15-mediated proliferation of the CTLL cell line and interferon gamma production by murine NK cells, which suggests a role in IL-15 transpresentation. Conversely, a full-length sIL-15Ralpha ectodomain released by tumor necrosis factor-alpha-converting enzyme (TACE)-dependent proteolysis inhibits IL-15 activity. Thus, a dual mechanism of sIL-15Ralpha generation exists in mice, giving rise to polypeptides with distinct properties, which regulate IL-15 function. |
| Databáze: | OpenAIRE |
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