Interleukin 15 receptor, alpha subunit explained

Interleukin 15 receptor, alpha subunit is a subunit of the interleukin 15 receptor that in humans is encoded by the IL15RA gene.

Structure

The IL-15 receptor is composed of three subunits: IL-15R alpha, CD122, and CD132. Two of these subunits, CD122 and CD132, are shared with the receptor for IL-2, but IL-2 receptor has an additional subunit (CD25). The shared subunits contain the cytoplasmic motifs required for signal transduction, and this forms the basis of many overlapping biological activities of IL15 and IL2, although in vivo the two cytokines have separate biological effects. This may be due to effects of the respective alpha chains, which are unique to each receptor, the kinetics and affinity of cytokine-cytokine receptor binding, or due to the availability and concentration of each cytokine.

Function

IL-15Ralpha specifically binds IL15 with very high affinity,^[1] and is capable of binding IL-15 independently of other subunits. It is suggested that this property allows IL-15 to be produced by one cell, endocytosed by another cell, and then presented to a third party cell.^[2]

This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported. The full length sequences of only two variants encoding distinct isoforms are available.

Isoforms

Several isoforms of the IL-15Ralpha protein have been detected. These isoforms can either result from alternative splicing of the mRNA encoding for the receptor or by shedding of the extra cellular domain of the receptor protein.

References

Further reading

• Giri JG, Kumaki S, Ahdieh M, Friend DJ, Loomis A, Shanebeck K, DuBose R, Cosman D, Park LS, Anderson DM . Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor . EMBO J. . 14 . 15 . 3654–63 . 1995 . 7641685 . 394440 . 10.1002/j.1460-2075.1995.tb00035.x .
• Jacob CO, Mykytyn K, Varcony T, Drabkin HA . Mapping of the interleukin 5 receptor gene to human chromosome 3 p25-p26 and to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem repeat sequences . Mamm. Genome . 4 . 8 . 435–9 . 1993 . 8104057 . 10.1007/BF00296817 . 7862651 .
• Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, Giri J, Copeland NG, Gilbert DJ, Jenkins NA . Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes . J. Biol. Chem. . 270 . 50 . 29862–9 . 1995 . 8530383 . 10.1074/jbc.270.50.29862 . free.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Dubois S, Magrangeas F, Lehours P, Raher S, Bernard J, Boisteau O, Leroy S, Minvielle S, Godard A, Jacques Y . Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression . J. Biol. Chem. . 274 . 38 . 26978–84 . 1999 . 10480910 . 10.1074/jbc.274.38.26978 . free .
• Pereno R, Giron-Michel J, Gaggero A, Cazes E, Meazza R, Monetti M, Monaco E, Mishal Z, Jasmin C, Indiveri F, Ferrini S, Azzarone B . IL-15/IL-15Ralpha intracellular trafficking in human melanoma cells and signal transduction through the IL-15Ralpha . Oncogene . 19 . 45 . 5153–62 . 2000 . 11064452 . 10.1038/sj.onc.1203873 . free .
• Mariner JM, Lantz V, Waldmann TA, Azimi N . Human T cell lymphotropic virus type I Tax activates IL-15R alpha gene expression through an NF-kappa B site . J. Immunol. . 166 . 4 . 2602–9 . 2001 . 11160322 . 10.4049/jimmunol.166.4.2602 . free .
• Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K . Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex . J. Immunol. . 167 . 1 . 1–5 . 2001 . 11418623 . 10.4049/jimmunol.167.1.1 . free .
• Wu TS, Lee JM, Lai YG, Hsu JC, Tsai CY, Lee YH, Liao NS . Reduced expression of Bcl-2 in CD8+ T cells deficient in the IL-15 receptor alpha-chain . J. Immunol. . 168 . 2 . 705–12 . 2002 . 11777964 . 10.4049/jimmunol.168.2.705 . free .
• Khan IA, Moretto M, Wei XQ, Williams M, Schwartzman JD, Liew FY . Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response . J. Exp. Med. . 195 . 11 . 1463–70 . 2002 . 12045244 . 2193543 . 10.1084/jem.20011915 .
• Kurowska M, Rudnicka W, Maślińska D, Maśliński W . Expression of IL-15 and IL-15 receptor isoforms in select structures of human fetal brain . Ann. N. Y. Acad. Sci. . 966 . 1 . 441–5 . 2002 . 12114302 . 10.1111/j.1749-6632.2002.tb04245.x . 2002NYASA.966..441K . 35501431 .
• Comes A, Di Carlo E, Musiani P, Rosso O, Meazza R, Chiodoni C, Colombo MP, Ferrini S . IFN-gamma-independent synergistic effects of IL-12 and IL-15 induce anti-tumor immune responses in syngeneic mice . Eur. J. Immunol. . 32 . 7 . 1914–23 . 2002 . 12115611 . 10.1002/1521-4141(200207)32:7<1914::AID-IMMU1914>3.0.CO;2-P . 46650793 . free .
• Bernard J, Harb C, Mortier E, Quéméner A, Meloen RH, Vermot-Desroches C, Wijdeness J, van Dijken P, Grötzinger J, Slootstra JW, Plet A, Jacques Y . Identification of an interleukin-15alpha receptor-binding site on human interleukin-15 . J. Biol. Chem. . 279 . 23 . 24313–22 . 2004 . 15039446 . 10.1074/jbc.M312458200 . free .
• Vámosi G, Bodnár A, Vereb G, Jenei A, Goldman CK, Langowski J, Tóth K, Mátyus L, Szöllösi J, Waldmann TA, Damjanovich S . IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells . Proc. Natl. Acad. Sci. U.S.A. . 101 . 30 . 11082–7 . 2004 . 15263076 . 503744 . 10.1073/pnas.0403916101 . 2004PNAS..10111082V . free .
• Mortier E, Bernard J, Plet A, Jacques Y . Natural, proteolytic release of a soluble form of human IL-15 receptor alpha-chain that behaves as a specific, high affinity IL-15 antagonist . J. Immunol. . 173 . 3 . 1681–8 . 2004 . 15265897 . 10.4049/jimmunol.173.3.1681 . free .

Notes and References

1. Giri JG, Ahdieh M, Eisenman J, Shanebeck K, Grabstein K, Kumaki S, Namen A, Park LS, Cosman D, Anderson D . Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15 . EMBO J. . 13 . 12 . 2822–30 . 1994 . 8026467 . 395163 . 10.1002/j.1460-2075.1994.tb06576.x .
2. Dubois S, Mariner J, Waldmann TA, Tagaya Y . IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells . Immunity . 17 . 5 . 537–47 . 2002 . 12433361 . 10.1016/s1074-7613(02)00429-6 . free . (primary source)