Cloning of the human IL‐13Rα1 chain and reconstitution with the IL‐4Rα of a functional IL‐4/IL‐13 receptor complex

Miloux, Brigitte; Laurent, Patrick; Bonnin, Odile; Lupker, Jan H.; Caput, Daniel; Vita, Natalio; Ferrara, Pascual

doi:10.1016/s0014-5793(96)01462-7

Cited by 200 publications

(84 citation statements)

References 28 publications

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“…IL-13 mediates these functions through interacting with its cognate receptor on hematopoietic and other cell types, but no functional receptors have been identified on human or mouse T-cells (7). The human IL-13 receptor (IL-13R) is a heterodimer composed of the interleukin-4 receptor ␣ chain (IL-4R␣) and an IL-13 binding protein, IL-13R␣1 (10). Although they only share 25% homology, IL-13 shares many functional properties with IL-4 as a result of the common IL-4R␣ component in their receptors.…”

Section: Il-13mentioning

confidence: 99%

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Kinetic Analysis of the Interleukin-13 Receptor Complex

Andrews

Holloway²,

Puddicombe

et al. 2002

Journal of Biological Chemistry

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Interleukin (IL)-13 is a key cytokine associated with the asthmatic phenotype. It signals via its cognate receptor, a complex of IL-13 receptor ␣1 chain (IL-13R␣1) with IL-4R␣; however, a second protein, IL-13R␣2, also binds IL-13. To determine the binding contributions of the individual components of the IL-13 receptor to IL-13, we have employed surface plasmon resonance and equilibrium binding assays to investigate the ligand binding characteristics of shIL-13R␣1, shIL-13R␣2, and IL-4R␣. shIL-13R␣1 bound IL-13 with moderate affinity (K D ‫؍‬ 37.8 ؎ 1.8 nM, n ‫؍‬ 10), whereas no binding was observed for hIL-4R␣. In contrast, shIL-13R␣2 produced a high affinity interaction with IL-13 (K D ‫؍‬ 2.49 ؎ 0.94 nM n ‫؍‬ 10). IL-13R␣2 exhibited the binding characteristics of a negative regulator with a fast association rate and an exceptional slow dissociation rate. Although IL-13 interacted weakly with IL-4R␣ on its own (K D > 50 M), the presence of hIL-4R␣ significantly increased the affinity of shIL-13R␣1 for IL-13 but had no effect on the binding affinity of IL-13R␣2. Detailed kinetic analyses of the binding properties of the heteromeric complexes suggested a sequential mechanism for the binding of IL-13 to its signaling receptor, in which IL-13 first binds to IL-13R␣1 and this then recruits IL-4R␣ to stabilize a high affinity interaction.

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Section: Il-13mentioning

confidence: 99%

“…A second IL-13 binding protein, IL-13R␣2, has also been identified. IL-13R␣2 shares a 37% homology with IL-13R␣1 and binds IL-13 with high affinity (50 pM) (10,(13)(14)(15). Despite this increased binding affinity, IL-13R␣2 is believed to be non-signaling and therefore may act as a "decoy" receptor.…”

Section: Il-13mentioning

confidence: 99%

Kinetic Analysis of the Interleukin-13 Receptor Complex

Andrews

Holloway²,

Puddicombe

et al. 2002

Journal of Biological Chemistry

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“…Their respective genes have been mapped to the X chromosome, and in vitro expression of IL-13R␣1 and IL-13R␣2 has revealed that they both specifically bind IL-13 (9 -14). IL-13R␣1 binds IL-13 with low affinity by itself, but, when paired with IL-4R␣, it binds IL-13 with high affinity and forms a functional IL-13 receptor which signals (12). In cells lacking the common ␥ chain, this receptor complex also serves as an alternative receptor for IL-4.…”

Section: Interleukin (Il)mentioning

confidence: 99%

A Novel Mechanism by Which Interferon-γ Can Regulate Interleukin (IL)-13 Responses

Daines

Hershey

2002

Journal of Biological Chemistry

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Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor ␣-1 chain (IL-13R␣1) binds IL-13 with low affinity, but does not signal. However, when IL-13R␣1 combines with IL-4 receptor ␣ (IL-4R␣), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13R␣2 alone binds IL-13 with high affinity, but does not signal and has been postulated to be a decoy receptor. Herein, we investigated the cellular localization of IL-13R␣2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13R␣2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-␥. Up-regulation of IL-13R␣2 surface expression in response to IFN-␥ was rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13R␣2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-␥ can regulate IL-13 responses.

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“…6,7 IL-13 mediates its effects via its cognate receptor, a heterodimer composed of the IL-13 binding protein, IL-13Ra1 and the Interleukin-4 receptor a chain (IL-4Ra). [8][9][10] The IL-13Ra1-IL-4Ra complex also acts as a receptor for IL-4, especially in cells lacking the common gamma chain (gc) that usually forms a complex with IL-4Ra to bind IL-4. 11,12 Binding of either IL-13 or IL-4 to the IL-13Ra1-IL-4Ra receptor complex initiates a phosphorylation cascade that results in STAT6 dimerization; STAT6 then translocates to the nucleus where it induces inflammatory gene expression.…”

Section: Introductionmentioning

confidence: 99%