ArticleNature chemical biology2012
LYP inhibits T-cell activation when dissociated from CSK.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- A Potent and Selective Quinolone-Based PTPN22 Inhibitor with Improved Immunotherapeutic Activity.Journal of medicinal chemistry · 2026Article
- An autoimmunity-associated allele ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- An Autoimmunity-associated allele ofbioRxiv : the preprint server for biology · 2025Article
- The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR.Scientific reports · 2025Article
- The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- The protein tyrosine phosphatase Lyp/PTPN22 drives TNFα-induced priming of superoxide anions production by neutrophils and arthritis.Free radical biology & medicine · 2025Article
- Structure-activity relationship studies and design of a PTPN22 inhibitor with enhanced isozyme selectivity and cellular efficacy.European journal of medicinal chemistry · 2025Article
- Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics.Frontiers in immunology · 2025Review
- Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.PLoS pathogens · 2024Article
- The genetics of Graves' disease.Reviews in endocrine & metabolic disorders · 2024Review
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation.Cancers · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- PTPN22 intron polymorphism rs1310182 (c.2054-852T>C) is associated with type 1 diabetes mellitus in patients of Armenian descent.PloS one · 2023Article
- PTPN22: structure, function, and developments in inhibitor discovery with applications for immunotherapy.Expert opinion on drug discovery · 2022Review
- SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.Scientific reports · 2022Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Lymphoid tyrosine phosphatase (LYP) and C-terminal Src kinase (CSK) are negative regulators of signaling mediated through the T-cell antigen receptor (TCR) and are thought to act in a cooperative manner when forming a complex. Here we studied the spatiotemporal dynamics of the LYP-CSK complex in T cells. We demonstrate that dissociation of this complex is necessary for recruitment of LYP to the plasma membrane, where it downmodulates TCR signaling. Development of a potent and selective chemical probe of LYP confirmed that LYP inhibits T-cell activation when removed from CSK. Our findings may explain the reduced TCR-mediated signaling associated with a single-nucleotide polymorphism that confers increased risk for certain autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, and results in expression of a mutant LYP that is unable to bind CSK. Our compound also represents a starting point for the development of a LYP-based treatment of autoimmunity.
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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.