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The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling

The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling
The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling
Interleukin-4 (IL-4) and Interleukin-13 (IL-13), key cytokines in the pathogenesis of allergic inflammatory disease, mediate their effects via a receptor composed of IL-13R?1 and IL-4R?. A third (decoy) receptor called IL-13R?2 regulates interleukin signaling through this receptor complex. We employed a variety of biophysical and cell-based techniques to decipher the role of this decoy receptor in mediating IL-4 signaling though the IL-4R?–IL-13R?1 receptor complex. Surface plasmon resonance (SPR) analysis showed that IL-13R?2 does not bind IL-4, and does not affect binding of IL-4 to IL-4R?. These results indicate that the extracellular domains of IL-4R? and IL-13R?2 are not involved in the regulation of IL-4 signaling by IL-13R?2. We next used a two-hybrid system to show that the cytoplasmic domains of IL-4R? and IL-13R?2 interact, and that the secondary structure of the IL-13R?2 intracellular domain is critical for this interaction. The cellular relevance of this interaction was next investigated. BEAS-2B bronchial epithelial cells that stably express full length IL-13R?2, or IL-13R?2 lacking its cytoplasmic domain, were established. Over expression of IL-13R?2 attenuated IL-4 and IL-13 mediated STAT6 phosphorylation. IL-13R?2 lacking its cytoplasmic domain continued to attenuate IL-13-mediated signaling, but had no effect on IL-4-mediated STAT6 signaling. Our results suggest that the physical interaction between the cytoplasmic domains of IL-13R?2 and IL-4R? regulates IL-4 signaling through the IL-4R?–IL-13R?1 receptor complex.



1742-2051
3009-3014
Andrews, Allison-Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Nordgren, Ida Karin
3ccc4429-3f5a-4b52-8d56-b24220b45bba
Campbell-Harding, Gemma
49a1dc97-d914-4a0f-94d2-406f7844f125
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2
Andrews, Allison-Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Nordgren, Ida Karin
3ccc4429-3f5a-4b52-8d56-b24220b45bba
Campbell-Harding, Gemma
49a1dc97-d914-4a0f-94d2-406f7844f125
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2

Andrews, Allison-Lynn, Nordgren, Ida Karin, Campbell-Harding, Gemma, Holloway, John W., Holgate, Stephen T., Davies, Donna E. and Tavassoli, Ali (2013) The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling. Molecular BioSystems, 9 (12), 3009-3014. (doi:10.1039/C3MB70298G). (PMID:24056919)

Record type: Article

Abstract

Interleukin-4 (IL-4) and Interleukin-13 (IL-13), key cytokines in the pathogenesis of allergic inflammatory disease, mediate their effects via a receptor composed of IL-13R?1 and IL-4R?. A third (decoy) receptor called IL-13R?2 regulates interleukin signaling through this receptor complex. We employed a variety of biophysical and cell-based techniques to decipher the role of this decoy receptor in mediating IL-4 signaling though the IL-4R?–IL-13R?1 receptor complex. Surface plasmon resonance (SPR) analysis showed that IL-13R?2 does not bind IL-4, and does not affect binding of IL-4 to IL-4R?. These results indicate that the extracellular domains of IL-4R? and IL-13R?2 are not involved in the regulation of IL-4 signaling by IL-13R?2. We next used a two-hybrid system to show that the cytoplasmic domains of IL-4R? and IL-13R?2 interact, and that the secondary structure of the IL-13R?2 intracellular domain is critical for this interaction. The cellular relevance of this interaction was next investigated. BEAS-2B bronchial epithelial cells that stably express full length IL-13R?2, or IL-13R?2 lacking its cytoplasmic domain, were established. Over expression of IL-13R?2 attenuated IL-4 and IL-13 mediated STAT6 phosphorylation. IL-13R?2 lacking its cytoplasmic domain continued to attenuate IL-13-mediated signaling, but had no effect on IL-4-mediated STAT6 signaling. Our results suggest that the physical interaction between the cytoplasmic domains of IL-13R?2 and IL-4R? regulates IL-4 signaling through the IL-4R?–IL-13R?1 receptor complex.



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e-pub ahead of print date: 17 September 2013
Published date: 1 December 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 357430
URI: http://eprints.soton.ac.uk/id/eprint/357430
ISSN: 1742-2051
PURE UUID: aa256881-9a59-4217-8a70-a6f57128facd
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Ali Tavassoli: ORCID iD orcid.org/0000-0002-7420-5063

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Date deposited: 07 Oct 2013 12:57
Last modified: 28 Oct 2023 01:56

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Contributors

Author: Allison-Lynn Andrews
Author: Ida Karin Nordgren
Author: Gemma Campbell-Harding
Author: Donna E. Davies ORCID iD
Author: Ali Tavassoli ORCID iD

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