ArticleThe Journal of biological chemistry2010
Autoimmune-associated PTPN22 R620W variation reduces phosphorylation of lymphoid phosphatase on an inhibitory tyrosine residue.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
- Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied in the past two decades.PloS one · 2012Pooled it
- Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan.Scientific reports · 2016Trial
- From pathogenesis to precision medicine in systemic lupus erythematosus: Emerging biomarkers and targeted interventions.iScience · 2026Review
- An autoimmunity-associated allele ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Idiopathic achalasia: unraveling the etiology and pathogenesis of an inflammatory disease.Gastroenterology report · 2026Review
- An Autoimmunity-associated allele ofbioRxiv : the preprint server for biology · 2025Article
- PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity.Science advances · 2025Article
- Whole-Exome Sequencing: Discovering Genetic Causes of Granulomatous Mastitis.International journal of molecular sciences · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.The Journal of biological chemistry · 2024Article
- Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.PLoS pathogens · 2024Article
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- Genetic Factors of Predisposition and Clinical Characteristics of Rheumatoid Arthritis in Russian Patients.Journal of personalized medicine · 2021Article
- De-coding genetic risk variants in type 1 diabetes.Immunology and cell biology · 2021Review
- Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency.Cellular & molecular immunology · 2021Review
- Influence ofFrontiers in immunology · 2021Review
- PTPN22 phosphorylation acts as a molecular rheostat for the inhibition of TCR signaling.Science signaling · 2020Article
- Phosphatase PTPN22 Regulates Dendritic Cell Homeostasis and cDC2 Dependent T Cell Responses.Frontiers in immunology · 2020Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
A missense C1858T single nucleotide polymorphism in the PTPN22 gene recently emerged as a major risk factor for human autoimmunity. PTPN22 encodes the lymphoid tyrosine phosphatase (LYP), which forms a complex with the kinase Csk and is a critical negative regulator of signaling through the T cell receptor. The C1858T single nucleotide polymorphism results in the LYP-R620W variation within the LYP-Csk interaction motif. LYP-W620 exhibits a greatly reduced interaction with Csk and is a gain-of-function inhibitor of signaling. Here we show that LYP constitutively interacts with its substrate Lck in a Csk-dependent manner. T cell receptor-induced phosphorylation of LYP by Lck on an inhibitory tyrosine residue releases tonic inhibition of signaling by LYP. The R620W variation disrupts the interaction between Lck and LYP, leading to reduced phosphorylation of LYP, which ultimately contributes to gain-of-function inhibition of T cell signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.