ArticleProceedings of the National Academy of Sciences of the United States of America1994
Cooperative interactions between the interleukin 2 receptor alpha and beta chains alter the interleukin 2-binding affinity of the receptor subunits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2006Trial
- Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1.The Journal of biological chemistry · 2026Article
- Review
- Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.Science (New York, N.Y.) · 2018Article
- Gamma chain receptor interleukins: evidence for positive selection driving the evolution of cell-to-cell communicators in the mammalian immune system.Journal of molecular evolution · 2005Article
- Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers.Clinical and experimental immunology · 2000Article
- Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: a fluorescence resonance energy transfer study.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- Understanding cytokine and growth factor receptor activation mechanisms.Critical reviews in biochemistry and molecular biologyReview
- Engineered interleukin-2 antagonists for the inhibition of regulatory T cells.Journal of immunotherapy (Hagerstown, Md. : 1997)Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interleukin 2 (IL-2) receptor (IL-2R) is a multisubunit receptor that includes three major IL-2 binding subunits, the IL-2R alpha, beta, and gamma chains. We have detected and analyzed cooperative interactions between the IL-2R alpha and beta chains (IL-2R alpha and IL-2R beta, respectively) in COS cells transfected with cDNAs encoding the IL-2R alpha, the IL-2R beta, or both cDNAs. We demonstrated that IL-2 F42A, an analog that fails to bind to the isolated IL-2R alpha subunit and would be predicted by the hierarchical affinity-conversion model to have impaired binding to cells expressing both chains, instead readily binds to the IL-2R alpha/beta heterodimer in COS cells. Furthermore, this binding is abolished by the antibody HIEI that separates the two IL-2R subunits. The monoclonal antibodies anti-Tac and Mik-beta 1 directed at the IL-2-binding sites on IL-2R alpha and IL-2R beta, respectively, block ligand binding to the heterodimer. This binding pattern is inconsistent with the strict hierarchical affinity-conversion model that mandates an initial binding of IL-2 to IL-2R alpha followed by binding of the IL-2/IL-2R alpha complex to IL-2R beta. Instead, our results support an alternative model of preformed complexes of IL-2R beta with other IL-2R subunits. In this alternative model, IL-2R alpha and -beta exist in part as preformed complexes in which the affinity of IL-2R beta for IL-2 is altered by the proximity of IL-2R alpha, through mechanisms that do not require the prior binding of IL-2 to IL-2R alpha.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.