This protein is located on the surface of immature blood-forming cells inbone marrow. One end of the protein resides outside the cell where it binds tocytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to formlymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes:T cells,B cells,innate lymphoid cells, andnatural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.
Cytokine receptor common subunit gamma also known asinterleukin-2 receptor subunit gamma orIL-2RG is aprotein that in humans is encoded by theIL2RGgene.[8] The human IL2RG gene is located on the long (q) arm of theX chromosome at position 13.1, frombase pair 70,110,279 to base pair 70,114,423.
IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)
Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmitsignals from one cell to another and direct programs ofcellular differentiation.
IL2RG plays a critical role in lymphocyte signal transduction in response toIL-4,IL-7,IL-9,IL-21,IL-15, andIL-2. Once eitherIL4-Rα,IL-7Rα,IL-9Rα,IL-21Rα,IL-2R orIL-15R has bound to their respective ligands, IL2RG is quickly recruited and forms aheterodimer with the cytoplasmic tail of the opposing receptor. After the heterodimer has formed, IL2RG then activatesJAK3, and the opposing receptor activatesJAK1. JAK1 and JAK3 thenphosphorylate both IL2RG and the opposing receptor's cytoplasmic tail. This phosphorylation allows for IL-2RG and its opposing receptor to recruit aSTAT protein. JAK3 and JAK1 subsequently phosphorylate the recruited STAT, allowing the STAT to form a dimer ortetramer with other phosphorylated STAT proteins. Finally, these dimer or STATs translocate to the nucleus, bind STAT motifs within the nuclear DNA, and induce transcription within specific genes.[12]
X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID).[13] Most of these mutations involve changes in one or a fewnucleotides (DNA building blocks) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein[citation needed] or no production of protein.[14] Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Affected people have no functional immunity and can die within months after birth without successfulbone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15,T-cell andNK cell populations respectively fail to develop.
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.[15]
Alterations in the immune response are involved inpathogenesis of many neuropsychiatric disorders includingschizophrenia. Distinct gene variants of a number of pro-inflammatory and chemotactic cytokines together with their receptors associate with this disorder. IL2RG represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. Over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathogenesis of this disorder.[16]
^Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, et al. (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits".Science.266 (5187):1045–7.Bibcode:1994Sci...266.1045M.doi:10.1126/science.7973659.PMID7973659.
Bamborough P, Hedgecock CJ, Richards WG (1995). "The interleukin-2 and interleukin-4 receptors studied by molecular modelling".Structure.2 (9):839–51.doi:10.1016/S0969-2126(94)00085-9.PMID7529123.
Clark PA, Lester T, Genet S, Jones AM, Hendriks R, Levinsky RJ, et al. (October 1995). "Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R gamma chain gene by single-strand conformation polymorphism analysis".Hum. Genet.96 (4):427–32.doi:10.1007/BF00191801.PMID7557965.S2CID29039832.
Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, et al. (August 1994). "Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency".J. Immunol.153 (3):1310–7.doi:10.4049/jimmunol.153.3.1310.PMID8027558.S2CID24092176.
Johnson K, Choi Y, Wu Z, Ciardelli T, Granzow R, Whalen C, et al. (1994). "Soluble IL-2 receptor beta and gamma subunits: ligand binding and cooperativity".Eur. Cytokine Netw.5 (1):23–34.PMID8049354.
Markiewicz S, Subtil A, Dautry-Varsat A, Fischer A, de Saint Basile G (May 1994). "Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing".Genomics.21 (1):291–3.doi:10.1006/geno.1994.1265.PMID8088810.
Kondo M, Takeshita T, Ishii N, Nakamura M, Watanabe S, Arai K, et al. (December 1993). "Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4".Science.262 (5141):1874–7.Bibcode:1993Sci...262.1874K.doi:10.1126/science.8266076.PMID8266076.
