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An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation
Within the IL10R1 gene two common variants are associated with certain diseases: SNP3, a serine-138-to-glycine mutation is in linkage disequilibrium with SNP4, a glycine-330-to-arginine mutation, both of which are considered loss-of-function alleles. However, the molecular consequence of G330R is un...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173877/ https://www.ncbi.nlm.nih.gov/pubmed/21654841 http://dx.doi.org/10.1038/gene.2011.12 |
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author | Finsterbusch, Michaela Khare, Vineeta Campregher, Christoph Evstatiev, Rayko Gasche, Christoph |
author_facet | Finsterbusch, Michaela Khare, Vineeta Campregher, Christoph Evstatiev, Rayko Gasche, Christoph |
author_sort | Finsterbusch, Michaela |
collection | PubMed |
description | Within the IL10R1 gene two common variants are associated with certain diseases: SNP3, a serine-138-to-glycine mutation is in linkage disequilibrium with SNP4, a glycine-330-to-arginine mutation, both of which are considered loss-of-function alleles. However, the molecular consequence of G330R is unknown. We investigated possible roles of G330R on the dynamics of IL10R1 surface expression and STAT phosphorylation. HeLa cells expressing the respective IL10R1 haplotype were stimulated with IL-10. Significant reduction of IL10R1 surface expression was observed after ligand-binding. Receptor expression remained low upon continuous incubation with IL-10. In contrast, when treated with an IL-10 pulse, IL10R1 surface expression returned to its resting state within 3 to 9 hours irrespective of the haplotype. STAT3 was rapidly phosphorylated both in cells with wildtype or variant IL10R1 and maintained phosphorylated when cells were cultured with IL-10. Upon IL-10 pulse, however, STAT3 phosphorylation declined rapidly in cells expressing IL10R1-G330R but not IL10R1-WT or S138G. Similar dynamics were observed with STAT1 phosphorylation at Tyr701. No differences in JAK1 activation were observed in cells with wildtype or variant IL10R1. Our results indicate that IL10R1-G330R does not alter surface expression but duration of STAT phosphorylation indicating that the position of G330 is important in stabilizing the STAT signal. |
format | Online Article Text |
id | pubmed-3173877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-31738772012-04-01 An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation Finsterbusch, Michaela Khare, Vineeta Campregher, Christoph Evstatiev, Rayko Gasche, Christoph Genes Immun Article Within the IL10R1 gene two common variants are associated with certain diseases: SNP3, a serine-138-to-glycine mutation is in linkage disequilibrium with SNP4, a glycine-330-to-arginine mutation, both of which are considered loss-of-function alleles. However, the molecular consequence of G330R is unknown. We investigated possible roles of G330R on the dynamics of IL10R1 surface expression and STAT phosphorylation. HeLa cells expressing the respective IL10R1 haplotype were stimulated with IL-10. Significant reduction of IL10R1 surface expression was observed after ligand-binding. Receptor expression remained low upon continuous incubation with IL-10. In contrast, when treated with an IL-10 pulse, IL10R1 surface expression returned to its resting state within 3 to 9 hours irrespective of the haplotype. STAT3 was rapidly phosphorylated both in cells with wildtype or variant IL10R1 and maintained phosphorylated when cells were cultured with IL-10. Upon IL-10 pulse, however, STAT3 phosphorylation declined rapidly in cells expressing IL10R1-G330R but not IL10R1-WT or S138G. Similar dynamics were observed with STAT1 phosphorylation at Tyr701. No differences in JAK1 activation were observed in cells with wildtype or variant IL10R1. Our results indicate that IL10R1-G330R does not alter surface expression but duration of STAT phosphorylation indicating that the position of G330 is important in stabilizing the STAT signal. 2011-06-09 2011-10 /pmc/articles/PMC3173877/ /pubmed/21654841 http://dx.doi.org/10.1038/gene.2011.12 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Finsterbusch, Michaela Khare, Vineeta Campregher, Christoph Evstatiev, Rayko Gasche, Christoph An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title | An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title_full | An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title_fullStr | An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title_full_unstemmed | An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title_short | An Intracytoplasmic IL-10 Receptor Variant Permits Rapid Reduction in STAT3 Activation |
title_sort | intracytoplasmic il-10 receptor variant permits rapid reduction in stat3 activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173877/ https://www.ncbi.nlm.nih.gov/pubmed/21654841 http://dx.doi.org/10.1038/gene.2011.12 |
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