Cutting Edge: The PTPN22 Allelic Variant Associated with Autoimmunity Impairs B Cell Signaling
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- Adrian F Arechiga
- Translational Research Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101
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- Tania Habib
- Translational Research Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101
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- Yantao He
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis IN 46202
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- Xian Zhang
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis IN 46202
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- Zhong-Yin Zhang
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis IN 46202
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- Andrew Funk
- Translational Research Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101
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- Jane H Buckner
- Translational Research Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101
書誌事項
- 公開日
- 2009-03
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.0713370
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>PTPN22 is a gene encoding the protein tyrosine phosphatase Lyp. A missense mutation changing residue 1858 from cytosine to thymidine (1858C/T) is associated with multiple autoimmune disorders. Studies have demonstrated that Lyp has an inhibitory effect on TCR signaling; however, the presence of autoantibodies in all of the diseases associated with the 1858T variant and recent evidence that Ca2+ flux is altered in B cells of 1858T carriers indicate a role for Lyp in B cell signaling. In this study we show that B cell signal transduction is impaired in individuals who express the variant. This defect in signaling is characterized by a deficit in proliferation, a decrease in phosphorylation of key signaling proteins, and is reversed by inhibition of Lyp. These findings suggest that the PTPN22 1858T variant alters BCR signaling and implicate B cells in the mechanism by which the PTPN22 1858T variant contributes to autoimmunity.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 182 (6), 3343-3347, 2009-03
Oxford University Press (OUP)
