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Gene Review

Il2rb  -  interleukin 2 receptor, beta chain

Mus musculus

Synonyms: CD122, High affinity IL-2 receptor subunit beta, IL-15 receptor beta chain, IL-15Rbeta, IL-2 receptor subunit beta, ...
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Disease relevance of Il2rb

  • The gene regulatory functions of the human IL-2 receptor (IL-2R) were reconstituted in transiently transfected hepatoma cells [1].
  • Interleukin-2 (IL-2)/IL-15 receptor beta (IL-15R beta)(-/-) mice were susceptible to infection with avirulent Salmonella enterica subsp. enterica serovar Choleraesuis, whereas IL-2(-/-) mice were resistant [2].
  • IL-2/IL-15R beta-deficient mice were susceptible to systemic HSV-2 infection compared with their heterozygous littermates [3].
  • Moreover, cDNA clones obtained from two murine neuroblastoma cell lines exhibited the same sequence as IL-2R beta cDNA from normal brain [4].
  • The IL-2R expression within the brain was not enhanced within 8 weeks following the intracerebral administration of rIL-2, suggesting that direct intracerebral infusion of rIL-2 may be safely used in the immunotherapy of brain tumors [5].

High impact information on Il2rb

  • The state involves an early block in tyrosine kinase activation, which predominantly inhibits calcium mobilization, and an independent mechanism that blocks signaling through the IL-2 receptor [6].
  • The third component, the gamma chain, of IL-2 receptor plays a pivotal role in formation of the full-fledged IL-2 receptor, together with the beta chain, the gamma chain participates in increasing the IL-2 binding affinity and intracellular signal transduction [7].
  • It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction [8].
  • Unlike the IL-2R alpha chain, the IL-2R beta chain contains a large cytoplasmic domain that shows no obvious tyrosine kinase motif [9].
  • These results and the similarities between FADD-/- mice and mice lacking the beta-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis [10].

Chemical compound and disease context of Il2rb


Biological context of Il2rb

  • Three critical events have been identified in the generation of the IL-2R signal for cell cycle progression, including heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain [16].
  • Studies of the biology of the IL-2 receptor have played a major part in establishing several of the fundamental principles that govern our current understanding of immunology [16].
  • Thus, distinct IL-2Rbeta chain signaling modules regulate T cell fate by stimulating growth and survival or by promoting apoptosis [17].
  • IL-2R beta-expressing cells were present in the fetal thymus with a CD25-CD44+Fc gamma R+HSA-/low TCR- phenotype, which is characteristic of progenitor cells [18].
  • Together, these results show that in addition to clonal deletion, self-recognition by immature thymocytes leads to phenotypic maturation of a small subset of thymocytes expressing IL-2R beta [19].

Anatomical context of Il2rb

  • Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells [20].
  • An alternative possibility is that the A and H regions of IL-2R beta are only redundant with respect to proliferation and that each region plays a unique and essential role in regulating other aspects of lymphocyte physiology [16].
  • One intriguing outcome of the IL-2R signaling studies performed in cell lines is the apparent functional redundancy of the A and H regions of IL-2R beta, and their corresponding downstream pathways, with respect to the proliferative response [16].
  • One possibility is that this redundancy is an unusual property of cultured cell lines and that primary lymphocytes require signals from both the A and the H regions of IL-2R beta for optimal proliferative responses in vivo [16].
  • We have investigated IEL and NK cells in mice deficient for IL-2R beta and describe here striking defects in the development of these cells [21].

Associations of Il2rb with chemical compounds

  • (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain [22].
  • Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis [23].
  • The unusual functional properties of the lpr cells, such as high A23187 dose requirement for maximal proliferation, low percentage of IL 2 receptor-expressing cells, and low levels of IL 2 secretion, suggested that these cells are arrested at a stage of development similar to that of 16-day fetal thymocytes and before adult L3T4-/Lyt-2- thymocytes [24].
  • The IL-2 receptor beta-chain (p70). Ligand binding ability of the cDNA-encoding membrane and secreted forms [25].
  • To compare the different activation pathways, we examined the effects of staurosporine (STAR) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), two protein kinase C (PKC) inhibitors, on the induction of interleukin secretion and IL-2R expression in these cells [26].

Physical interactions of Il2rb

  • Proteins with bulky or basic substitutions at residue D34 were weak antagonists due to severely reduced IL-2 binding and their reduced binding paralleled their defects in IL-2R activation [27].
  • The Tg CD8(+) T cells can bind the granulocyte-macrophage colony-stimulating GM-CSF produced by antigen stimulation, but the GM-CSF binding results in delivery of an IL-2R signal [28].

Enzymatic interactions of Il2rb

  • (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2Rbeta (which contains Y338) fail to phosphorylate Shc [22].

Regulatory relationships of Il2rb

  • We have confirmed that F42A does not bind to the IL-2R alpha chain when expressed alone on MT-1 cells or in the presence of the large or small excess of IL-2R beta chains present on either YT-1 cells or forskolin-induced YT-1 cells, respectively [29].
  • IL-4 induces IL-2 receptor p75 beta-chain gene expression and IL-2-dependent proliferation in mouse T lymphocytes [30].
  • High-affinity IL 2R induced in the complete absence of IL 2 were unable to transmit a proliferative response unless exposed to extremely high concentrations of IL 2 [31].
  • Activated T cells in IL-2R beta-deficient mice expressed normal levels of Fas antigen and underwent normal apoptosis in response to induction with anti-Fas mAb [32].
  • Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal [20].

Other interactions of Il2rb

  • Correspondingly, Stat5a-/- splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2R beta/gamma(c) receptors [33].
  • IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain [34].
  • The anti-IgM induces IL-2R alpha chain expression, whereas each of the two cytokines induces IL-2R beta chain expression in a dose-dependent manner [35].
  • The cytoplasmic region of the IL-2R beta c chain required for activation of Stat5 is mapped within the carboxyl-terminal 147 amino acids [36].
  • In addition, IL-4 increased the level of IL-2R beta expression in thymocytes [30].

Analytical, diagnostic and therapeutic context of Il2rb


  1. The action of interleukin-2 receptor subunits defines a new type of signaling mechanism for hematopoietin receptors in hepatic cells and fibroblasts. Morella, K.K., Lai, C.F., Kumaki, S., Kumaki, N., Wang, Y., Bluman, E.M., Witthuhn, B.A., Ihle, J.N., Giri, J., Gearing, D.P. J. Biol. Chem. (1995) [Pubmed]
  2. Mice lacking interleukin-2 (IL-2)/IL-15 receptor beta chain are susceptible to infection with avirulent Salmonella enterica subsp. enterica serovar choleraesuis but mice lacking IL-2 are resistant. Nishimura, H., Tagaya, M., Tsunobuchi, H., Suzuki, H., Nakashima, I., Yoshikai, Y. Infect. Immun. (2001) [Pubmed]
  3. A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus. Tsunobuchi, H., Nishimura, H., Goshima, F., Daikoku, T., Suzuki, H., Nakashima, I., Nishiyama, Y., Yoshikai, Y. Virology (2000) [Pubmed]
  4. Molecular cloning of a partial cDNA of the interleukin-2 receptor-beta in normal mouse brain: in situ localization in the hippocampus and expression by neuroblastoma cells. Petitto, J.M., Huang, Z. Brain Res. (1994) [Pubmed]
  5. Murine intracerebral interleukin-2 injection: pathological and immunological effects. Yamasaki, T., Kikuchi, H., Paine, J.T., Yamashita, J., Miyatake, S., Iwasaki, K., Kobayashi, H., Namba, Y., Hanaoka, M. J. Neurosurg. (1989) [Pubmed]
  6. T cell anergy. Schwartz, R.H. Annu. Rev. Immunol. (2003) [Pubmed]
  7. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Ohbo, K., Nakamura, M., Takeshita, T. Annu. Rev. Immunol. (1996) [Pubmed]
  8. The IL-2 receptor complex: its structure, function, and target genes. Minami, Y., Kono, T., Miyazaki, T., Taniguchi, T. Annu. Rev. Immunol. (1993) [Pubmed]
  9. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Hatakeyama, M., Mori, H., Doi, T., Taniguchi, T. Cell (1989) [Pubmed]
  10. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Zhang, J., Cado, D., Chen, A., Kabra, N.H., Winoto, A. Nature (1998) [Pubmed]
  11. Effects of pyocyanine, a blue pigment from Pseudomonas aeruginosa, on separate steps of T cell activation: interleukin 2 (IL 2) production, IL 2 receptor formation, proliferation and induction of cytolytic activity. Mühlradt, P.F., Tsai, H., Conradt, P. Eur. J. Immunol. (1986) [Pubmed]
  12. Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. Kimura, Y., Takeshita, T., Kondo, M., Ishii, N., Nakamura, M., Van Snick, J., Sugamura, K. Int. Immunol. (1995) [Pubmed]
  13. The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowel disease in Janus family tyrosine kinase 3(-/-) and IL-2 receptor gamma(-/-) mice. Murata, Y., Yamashita, A., Saito, T., Sugamura, K., Hamuro, J. Int. Immunol. (2002) [Pubmed]
  14. Glycosylation processing inhibition by castanospermine prevents experimental autoimmune encephalomyelitis by interference with IL-2 receptor signal transduction. Walter, S., Fassbender, K., Gulbins, E., Liu, Y., Rieschel, M., Herten, M., Bertsch, T., Engelhardt, B. J. Neuroimmunol. (2002) [Pubmed]
  15. Testosterone receptor blockade restores cellular immunity in male mice after burn injury. Messingham, K.A., Messingham, K.A., Shirazi, M., Duffner, L.A., Duffner, L.A., Emanuele, M.A., Kovacs, E.J., Kovacs, E.J., Kovacs, E.J., Kovacs, E.J. J. Endocrinol. (2001) [Pubmed]
  16. Biology of the interleukin-2 receptor. Nelson, B.H., Willerford, D.M. Adv. Immunol. (1998) [Pubmed]
  17. Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death. Van Parijs, L., Refaeli, Y., Lord, J.D., Nelson, B.H., Abbas, A.K., Baltimore, D. Immunity (1999) [Pubmed]
  18. Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. Leclercq, G., Debacker, V., de Smedt, M., Plum, J. J. Exp. Med. (1996) [Pubmed]
  19. Induction of interleukin 2 receptor beta chain expression by self-recognition in the thymus. Hanke, T., Mitnacht, R., Boyd, R., Hünig, T. J. Exp. Med. (1994) [Pubmed]
  20. Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation. Nelson, B.H., Lord, J.D., Greenberg, P.D. Nature (1994) [Pubmed]
  21. Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain. Suzuki, H., Duncan, G.S., Takimoto, H., Mak, T.W. J. Exp. Med. (1997) [Pubmed]
  22. Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling. Ravichandran, K.S., Igras, V., Shoelson, S.E., Fesik, S.W., Burakoff, S.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  23. Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain. Adachi, M., Sekiya, M., Torigoe, T., Takayama, S., Reed, J.C., Miyazaki, T., Minami, Y., Taniguchi, T., Imai, K. Blood (1996) [Pubmed]
  24. Interleukin 2 responses of lpr and normal L3T4-/Lyt-2- T cells induced by TPA plus A23187. Katagiri, K., Katagiri, T., Eisenberg, R.A., Ting, J., Cohen, P.L. J. Immunol. (1987) [Pubmed]
  25. The IL-2 receptor beta-chain (p70). Ligand binding ability of the cDNA-encoding membrane and secreted forms. Tsudo, M., Karasuyama, H., Kitamura, F., Tanaka, T., Kubo, S., Yamamura, Y., Tamatani, T., Hatakeyama, M., Taniguchi, T., Miyasaka, M. J. Immunol. (1990) [Pubmed]
  26. Contrasting effects of the protein kinase C inhibitor staurosporine on the interleukin-1 and phorbol ester activation pathways in the EL4-6.1 thymoma cell line. Dornand, J., Bouaboula, M., d'Angeac, A.D., Favero, J., Shire, D., Casellas, P. J. Cell. Physiol. (1992) [Pubmed]
  27. Receptor antagonist and selective agonist derivatives of mouse interleukin-2. Zurawski, S.M., Zurawski, G. EMBO J. (1992) [Pubmed]
  28. Enhanced signaling through the IL-2 receptor in CD8+ T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death. Cheng, L.E., Ohlén, C., Nelson, B.H., Greenberg, P.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. Unexpected effects of the IL-2 receptor alpha subunit on high affinity IL-2 receptor assembly and function detected with a mutant IL-2 analog. Kuziel, W.A., Ju, G., Grdina, T.A., Greene, W.C. J. Immunol. (1993) [Pubmed]
  30. IL-4 induces IL-2 receptor p75 beta-chain gene expression and IL-2-dependent proliferation in mouse T lymphocytes. Casey, L.S., Lichtman, A.H., Boothby, M. J. Immunol. (1992) [Pubmed]
  31. T cell activation in the absence of interleukin 2 (IL 2) results in the induction of high-affinity IL 2 receptor unable to transmit a proliferative signal. Proust, J.J., Shaper, N.L., Buchholz, M.A., Nordin, A.A. Eur. J. Immunol. (1991) [Pubmed]
  32. Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice. Suzuki, H., Hayakawa, A., Bouchard, D., Nakashima, I., Mak, T.W. Int. Immunol. (1997) [Pubmed]
  33. An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. Nakajima, H., Liu, X.W., Wynshaw-Boris, A., Rosenthal, L.A., Imada, K., Finbloom, D.S., Hennighausen, L., Leonard, W.J. Immunity (1997) [Pubmed]
  34. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain. Wang, H.Y., Paul, W.E., Keegan, A.D. Immunity (1996) [Pubmed]
  35. Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth. Nakanishi, K., Hirose, S., Yoshimoto, T., Ishizashi, H., Hiroishi, K., Tanaka, T., Kono, T., Miyasaka, M., Taniguchi, T., Higashino, K. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  36. Activation of Stat5 by interleukin 2 requires a carboxyl-terminal region of the interleukin 2 receptor beta chain but is not essential for the proliferative signal transmission. Fujii, H., Nakagawa, Y., Schindler, U., Kawahara, A., Mori, H., Gouilleux, F., Groner, B., Ihle, J.N., Minami, Y., Miyazaki, T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  37. Normal regulatory alpha/beta T cells effectively eliminate abnormally activated T cells lacking the interleukin 2 receptor beta in vivo. Suzuki, H., Zhou, Y.W., Kato, M., Mak, T.W., Nakashima, I. J. Exp. Med. (1999) [Pubmed]
  38. In vivo and in vitro expression of an interleukin 2 receptor by murine B and T lymphocytes. Finkelman, F.D., Malek, T.R., Shevach, E.M., Mond, J.J. J. Immunol. (1986) [Pubmed]
  39. Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence on interleukin-2 receptor alpha, beta and gamma chain expression for T cell growth. Chastagner, P., Moreau, J.L., Jacques, Y., Tanaka, T., Miyasaka, M., Kondo, M., Sugamura, K., Thèze, J. Eur. J. Immunol. (1996) [Pubmed]
  40. Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor. Gouilleux, F., Moritz, D., Humar, M., Moriggl, R., Berchtold, S., Groner, B. Endocrinology (1995) [Pubmed]
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