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Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction

Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction
Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction

IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Ralpha2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Ralpha2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Ralpha2 may have some signalling capabilities, and a soluble form of IL-13Ralpha2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Ralpha2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Ralpha2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Ralpha2 with IL-4Ralpha appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Ralpha2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Ralpha and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2.

asthma, cytokine receptor, interleukin 4 (IL-4), interleukin 13 (IL-13), interleukin 13 receptor ?-chain 1 (IL-13R?1), signal transduction
0300-5127
873-876
Andrews, Allison-Lynn
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Nordgren, Ida Karin
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Kirby, Isabelle
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Holloway, John W
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Holgate, Stephen T
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Davies, Donna E
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Tavassoli, Ali
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Andrews, Allison-Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Nordgren, Ida Karin
f7d821ab-ba6c-4286-b439-f758909b2d61
Kirby, Isabelle
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Holloway, John W
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Holgate, Stephen T
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Davies, Donna E
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Tavassoli, Ali
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Andrews, Allison-Lynn, Nordgren, Ida Karin, Kirby, Isabelle, Holloway, John W, Holgate, Stephen T, Davies, Donna E and Tavassoli, Ali (2009) Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction. Biochemical Society Transactions, 37 (Pt 4), 873-876. (doi:10.1042/BST0370873).

Record type: Article

Abstract

IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Ralpha2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Ralpha2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Ralpha2 may have some signalling capabilities, and a soluble form of IL-13Ralpha2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Ralpha2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Ralpha2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Ralpha2 with IL-4Ralpha appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Ralpha2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Ralpha and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2.

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Published date: August 2009
Keywords: asthma, cytokine receptor, interleukin 4 (IL-4), interleukin 13 (IL-13), interleukin 13 receptor ?-chain 1 (IL-13R?1), signal transduction
Organisations: Chemistry, Human Development & Health, Chemical Biology Group, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 158657
URI: https://eprints.soton.ac.uk/id/eprint/158657
ISSN: 0300-5127
PURE UUID: 4d506470-0048-4a2c-94d8-3652cff39518
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: 25 Jun 2010 09:21
Last modified: 29 Oct 2019 02:11

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Contributors

Author: Allison-Lynn Andrews
Author: Ida Karin Nordgren
Author: Isabelle Kirby
Author: John W Holloway ORCID iD
Author: Donna E Davies ORCID iD
Author: Ali Tavassoli ORCID iD

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