IL2RB explained

Interleukin-2 receptor subunit beta is a protein that in humans is encoded by the IL2RB gene.^[1] Also known as CD122; IL15RB; P70-75.^[1]

Function

The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. The low affinity form is a monomer of the alpha subunit (also called CD25) and is not involved in signal transduction. The intermediate affinity form consists of a gamma/beta subunit heterodimer, while the high affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. The protein encoded by this gene represents the beta subunit and is a type I membrane protein.^[1]

This protein also forms one of the three subunits of the IL-15 receptor.

Activation of the receptor increases proliferation of CD8+ effector T cells.^[2]

Interactions

IL2RB has been shown to interact with:

• CISH,^[3]
• HGS,^[4]
• Janus kinase 1,^{[5] [6] [7] [8] [9]} and
• SHC1.^{[10] [11]}

See also

• IL-2 receptor
• IL-15 receptor

Further reading

• Ellery JM, Nicholls PJ . Alternate signalling pathways from the interleukin-2 receptor . Cytokine Growth Factor Rev. . 13 . 1 . 27–40 . 2002 . 11750878 . 10.1016/S1359-6101(01)00023-5 .
• Purvis SF, Georges DL, Williams TM, Lederman MM . Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat cells stably expressing the human immunodeficiency virus Tat protein . Cell. Immunol. . 144 . 1 . 32–42 . 1992 . 1394441 . 10.1016/0008-8749(92)90223-C .
• Torigoe T, Saragovi HU, Reed JC . Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line . Proc. Natl. Acad. Sci. U.S.A. . 89 . 7 . 2674–8 . 1992 . 1557373 . 48724 . 10.1073/pnas.89.7.2674 . 1992PNAS...89.2674T . free .
• Maslinski W, Remillard B, Tsudo M, Strom TB . Interleukin-2 (IL-2) induces tyrosine kinase-dependent translocation of active raf-1 from the IL-2 receptor into the cytosol . J. Biol. Chem. . 267 . 22 . 15281–4 . 1992 . 10.1016/S0021-9258(19)49530-6 . 1639773 . free .
• Miyazaki T, Maruyama M, Yamada G, Hatakeyama M, Taniguchi T . The integrity of the conserved 'WS motif' common to IL-2 and other cytokine receptors is essential for ligand binding and signal transduction . EMBO J. . 10 . 11 . 3191–7 . 1991 . 1915291 . 453042 . 10.1002/j.1460-2075.1991.tb04881.x.
• Shibuya H, Yoneyama M, Nakamura Y, Harada H, Hatakeyama M, Minamoto S, Kono T, Doi T, White R, Taniguchi T . The human interleukin-2 receptor beta-chain gene: genomic organization, promoter analysis and chromosomal assignment . Nucleic Acids Res. . 18 . 13 . 3697–703 . 1990 . 1973832 . 331067 . 10.1093/nar/18.13.3697 .
• Hatakeyama M, Kono T, Kobayashi N, Kawahara A, Levin SD, Perlmutter RM, Taniguchi T . Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association . Science . 252 . 5012 . 1523–8 . 1991 . 2047859 . 10.1126/science.2047859 . 1991Sci...252.1523H . 41503548 .
• Mills GB, May C, McGill M, Fung M, Baker M, Sutherland R, Greene WC . Interleukin 2-induced tyrosine phosphorylation. Interleukin 2 receptor beta is tyrosine phosphorylated . J. Biol. Chem. . 265 . 6 . 3561–7 . 1990 . 10.1016/S0021-9258(19)39806-0 . 2303462 . free .
• Oyaizu N, Chirmule N, Kalyanaraman VS, Hall WW, Pahwa R, Shuster M, Pahwa S . Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA . Proc. Natl. Acad. Sci. U.S.A. . 87 . 6 . 2379–83 . 1990 . 2315327 . 53690 . 10.1073/pnas.87.6.2379 . 1990PNAS...87.2379O . free .
• Gnarra JR, Otani H, Wang MG, McBride OW, Sharon M, Leonard WJ . Human interleukin 2 receptor beta-chain gene: chromosomal localization and identification of 5' regulatory sequences . Proc. Natl. Acad. Sci. U.S.A. . 87 . 9 . 3440–4 . 1990 . 2333293 . 53916 . 10.1073/pnas.87.9.3440 . 1990PNAS...87.3440G . free .
• Tsudo M, Kitamura F, Miyasaka M . Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies . Proc. Natl. Acad. Sci. U.S.A. . 86 . 6 . 1982–6 . 1989 . 2467293 . 286829 . 10.1073/pnas.86.6.1982 . 1989PNAS...86.1982T . free .
• Hatakeyama M, Tsudo M, Minamoto S, Kono T, Doi T, Miyata T, Miyasaka M, Taniguchi T . Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's . Science . 244 . 4904 . 551–6 . 1989 . 2785715 . 10.1126/science.2785715 . 1989Sci...244..551H .
• Kornfeld H, Cruikshank WW, Pyle SW, Berman JS, Center DM . Lymphocyte activation by HIV-1 envelope glycoprotein . Nature . 335 . 6189 . 445–8 . 1988 . 2843775 . 10.1038/335445a0 . 1988Natur.335..445K . 4326650 .
• Leonard WJ, Donlon TA, Lebo RV, Greene WC . Localization of the gene encoding the human interleukin-2 receptor on chromosome 10 . Science . 228 . 4707 . 1547–9 . 1985 . 3925551 . 10.1126/science.3925551 . 1985Sci...228.1547L .
• Bamborough P, Hedgecock CJ, Richards WG . The interleukin-2 and interleukin-4 receptors studied by molecular modelling . Structure . 2 . 9 . 839–51 . 1994 . 7529123 . 10.1016/S0969-2126(94)00085-9 . free .
• Minami Y, Nakagawa Y, Kawahara A, Miyazaki T, Sada K, Yamamura H, Taniguchi T . Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway . Immunity . 2 . 1 . 89–100 . 1995 . 7600304 . 10.1016/1074-7613(95)90081-0 . free .
• 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.
• Kirken RA, Rui H, Evans GA, Farrar WL . Characterization of an interleukin-2 (IL-2)-induced tyrosine phosphorylated 116-kDa protein associated with the IL-2 receptor beta-subunit . J. Biol. Chem. . 268 . 30 . 22765–70 . 1993 . 10.1016/S0021-9258(18)41592-X . 7693677 . free .
• Puri RK, Leland P, Aggarwal BB . Constitutive expression of human immunodeficiency virus type 1 tat gene inhibits interleukin 2 and interleukin 2 receptor expression in a human CD4+ T lymphoid (H9) cell line . AIDS Res. Hum. Retroviruses . 11 . 1 . 31–40 . 1995 . 7734194 . 10.1089/aid.1995.11.31 .
• Miyazaki T, Liu ZJ, Kawahara A, Minami Y, Yamada K, Tsujimoto Y, Barsoumian EL, Permutter RM, Taniguchi T . Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation . Cell . 81 . 2 . 223–31 . 1995 . 7736574 . 10.1016/0092-8674(95)90332-1 . free .

Notes and References

1. Web site: Entrez Gene: IL2RB interleukin 2 receptor, beta.
2. Boyman O, Sprent J . The role of interleukin-2 during homeostasis and activation of the immune system . Nat Rev Immunol . 12 . 3 . 180–190 . February 17, 2012 . 10.1038/nri3156 . 22343569. 22680847 .
3. Aman MJ, Migone TS, Sasaki A, Ascherman DP, ((Zhu Mh)), Soldaini E, Imada K, Miyajima A, Yoshimura A, Leonard WJ . CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling . J. Biol. Chem. . 274 . 42 . 30266–72 . October 1999 . 10514520 . 10.1074/jbc.274.42.30266. free .
4. Yamashita Y, Kojima K, Tsukahara T, Agawa H, Yamada K, Amano Y, Kurotori N, Tanaka N, Sugamura K, Takeshita T . Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor beta-chain . J. Cell Sci. . 121 . Pt 10 . 1727–38 . May 2008 . 18445679 . 10.1242/jcs.024455 . free .
5. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN . Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits . Science . 266 . 5187 . 1045–7 . November 1994 . 7973659 . 10.1126/science.7973659. 1994Sci...266.1045M .
6. Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O . Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID . Science . 266 . 5187 . 1042–5 . November 1994 . 7973658 . 10.1126/science.7973658. 1994Sci...266.1042R .
7. Usacheva A, Kotenko S, Witte MM, Colamonici OR . Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors . J. Immunol. . 169 . 3 . 1302–8 . August 2002 . 12133952 . 10.4049/jimmunol.169.3.1302. free .
8. Zhu MH, Berry JA, Russell SM, Leonard WJ . Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta . J. Biol. Chem. . 273 . 17 . 10719–25 . April 1998 . 9553136 . 10.1074/jbc.273.17.10719. free .
9. Migone TS, Rodig S, Cacalano NA, Berg M, Schreiber RD, Leonard WJ . Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation . Mol. Cell. Biol. . 18 . 11 . 6416–22 . November 1998 . 9774657 . 109227 . 10.1128/mcb.18.11.6416.
10. Delespine-Carmagnat M, Bouvier G, Bertoglio J . Association of STAT1, STAT3 and STAT5 proteins with the IL-2 receptor involves different subdomains of the IL-2 receptor beta chain . Eur. J. Immunol. . 30 . 1 . 59–68 . January 2000 . 10602027 . 10.1002/1521-4141(200001)30:1<59::AID-IMMU59>3.0.CO;2-1 . 40742391 .
11. Ravichandran KS, Burakoff SJ . The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation . J. Biol. Chem. . 269 . 3 . 1599–602 . January 1994 . 10.1016/S0021-9258(17)42066-7 . 8294403 . free .