Molecular cloning and expression of cDNAs for the human interleukin-2 receptor

Leonard, Warren J.; Depper, Joel M.; Crabtree, Gerald R.; Rudikoff, Stuart; Pumphrey, Janet G.; Robb, Richard J.; Krönke, Martin; Svetlik, Penny B.; Peffer, Nancy J.; Waldmann, Thomas A.; Greene, Warner C.

doi:10.1038/311626a0

Cited by 829 publications

(297 citation statements)

References 38 publications

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“…The IL-2 receptor family comprises three single-pass transmembrane proteins, IL-2Ra (p55, CD25), IL-2Rb (p75, CD122), and IL-2Rg (p64, CD132) (Robb et al 1981(Robb et al , 1984bLeonard et al 1984Leonard et al , 1985Greene et al 1986;Hatakeyama et al 1989;Tsudo et al 1990;Takeshita et al 1992;Noguchi et al 1993). IL-2Ra is present at low concentrations on T cells and is expressed along with IL-2 following TCR activation, forming a transient autocrine/paracrine signaling loop.…”

Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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Section: Ligand and Receptor Biologymentioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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“…At least in the case of IL-2Rb, phosphorylation of some of these tyrosine residues creates docking sites for the recruitment of signaling molecules (Friedmann et al, 1996;Fujii et al, 1995;Goldsmith et al, 1995;Ravichandran and Burako , 1994). In contrast, IL-2Ra has a short cytoplasmic domain (only 13 amino acids); it mainly contributes to IL-2 binding a nity and is unlikely to contribute to signaling per se (Leonard et al, 1984;Nikaido et al, 1984).…”

Section: How Does Il-2 Transduce Its Signals?mentioning

confidence: 99%

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

2000

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“…CD122 is common to both the IL-2R and IL-15R, with each receptor having a unique a chain that defines receptor specificity (IL-2Ra and IL-15Ra, respectively). Unlike CD122, the role of CD25 appears to be confined to increasing binding affinity (KD *10 -9 -10 -11 M) and it is postulated that the short cytoplasmic domain is unlikely to contribute to signaling [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

IL‐2Rβ links IL‐2R signaling with Foxp3 expression

2007

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Immunological tolerance to self antigens is a tightly regulated process. Recent work has demonstrated that the forkhead family member Foxp3 is a critical element in the differentiation and function of mouse CD4 + CD25 + regulatory T cells (Treg). Recent work has suggested an important role for IL-2 in the development and maintenance of Treg. To directly assess the effect of IL-2 signaling on Treg development and function, we analyzed mice that were genetically deficient in components of the IL-2 receptor (IL-2R). Mice lacking CD25 (IL-2Ra) displayed a slight decrease in Treg within the thymus, while peripheral numbers are unchanged. In contrast, we found that mice deficient in CD122 (IL-2Rb) had a profound reduction in both thymic and peripheral Treg, coinciding with more rapid development of a fatal lymphoproliferative disease. Expression of a Foxp3 transgene restored Treg and protected against the onset of autoimmunity. Thus, a signal mediated by IL-2Rb is essential for the development and homeostasis of Foxp3 + Treg in vivo.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2007/37101_s.pdf IntroductionPeripheral tolerance to self antigens is regulated, in part, by a population of CD4 + CD25 + Foxp3 + regulatory T cells (Treg). Genetic lesions in the Foxp3 gene (the scurfy mutant mouse or human patients with immune dysfunction/polyendocrinopathy/enteropathy/X-linked syndrome) lack Treg and develop a fatal autoimmune lymphoproliferative disease [1][2][3][4][5][6][7]. A similar, but less severe, phenotype is observed in mice deficient in IL-2 and components of its receptor complex, . Thus, disrupting the IL-2R signaling pathway results in severe T cell-mediated autoimmunity rather than immune deficiency, indicating a significant role for IL-2R signaling in Treg development and function.Signaling through the IL-2R complex is initiated by ligand-induced heterodimerization of CD122 and CD132, which activates the associated tyrosine kinases JAK1 and JAK3. Since it has previously been shown that a covalently linked JAK3 molecule can functionally replace the cytoplasmic domain of CD132, the role of CD132 in IL-2R signaling appears to be restricted to the recruitment of JAK3 [13]. By contrast, CD122 provides essential docking sites for at least two major downstream signaling mediators, the adaptor protein Shc and the transcription factor STAT5. CD122 is common to both the IL-2R and IL-15R, with each receptor having a unique a chain that defines receptor specificity (IL-2Ra and IL-15Ra, respectively). Unlike CD122, the role of CD25 appears to be confined to increasing binding affinity (KD *10 -9 -10 -11 M) and it is postulated that the short cytoplasmic domain is unlikely to contribute to signaling [13][14][15][16][17][18].Several lines of evidence suggest that IL-2 is essential for the homeostatic proliferation of Treg. For example, bone marrow chimera studies showed that IL-2 production by non-Treg is required for Treg maintenance [19]. In addition, treatment of mice with...

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Molecular cloning and expression of cDNAs for the human interleukin-2 receptor

Cited by 829 publications

References 38 publications

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

IL‐2Rβ links IL‐2R signaling with Foxp3 expression

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