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dc.contributor.authorChang, Hui-Hsin
dc.contributor.authorTai, Tzong-Shyuan
dc.contributor.authorLu, Bing
dc.contributor.authorIannaccone, Christine
dc.contributor.authorCernadas, Manuela
dc.contributor.authorWeinblatt, Michael Elliott
dc.contributor.authorShadick, Nancy Ann
dc.contributor.authorMiaw, Shi-Chuen
dc.contributor.authorHo, I-Cheng
dc.date.accessioned2013-02-19T20:55:20Z
dc.date.issued2012
dc.identifier.citationChang, Hui-Hsin, Tzong-Shyuan Tai, Bing Lu, Christine Iannaccone, Manuela Cernadas, Michael Weinblatt, Nancy Shadick, Shi-Chuen Miaw, and I-Cheng Ho. 2012. PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis. PLoS ONE 7(3): e33067.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10313340
dc.description.abstractPTPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease. The effect of the R-to-W conversion on the phosphatase activity of PTPN22 protein and the impact of the minor T allele of the C1858T SNP on the activation of T cells has remained controversial. In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood. Here we report the identification of an alternative splice form of human PTPN22, namely PTPN22.6. It lacks the nearly entire phosphatase domain and can function as a dominant negative isoform of the full length PTPN22. Although conversion of R620 to W620 in the context of PTPN22.1 attenuated T cell activation, expression of the tryptophan variant of PTPN22.6 reciprocally led to hyperactivation of human T cells. More importantly, the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis. Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0033067en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299735/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectgeneticsen_US
dc.subjectimmunologyen_US
dc.subjectimmunityen_US
dc.subjectmedicineen_US
dc.subjectclinical immunologyen_US
dc.subjectautoimmune diseasesen_US
dc.subjectdiagnostic medicineen_US
dc.subjectpathologyen_US
dc.subjectgeneral pathologyen_US
dc.subjectrheumatologyen_US
dc.titlePTPN22.6, a Dominant Negative Isoform of PTPN22 and Potential Biomarker of Rheumatoid Arthritisen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWeinblatt, Michael Elliott
dc.date.available2013-02-19T20:55:20Z
dc.identifier.doi10.1371/journal.pone.0033067*
dash.contributor.affiliatedTai, Tzong-Shyuan
dash.contributor.affiliatedHo, I-Cheng
dash.contributor.affiliatedChang, Hui-Hsin
dash.contributor.affiliatedShadick, Nancy
dash.contributor.affiliatedLu, Bing
dash.contributor.affiliatedWeinblatt, Michael
dash.contributor.affiliatedCernadas, Manuela


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