ArticleProceedings of the National Academy of Sciences of the United States of America2011
Enhanced T-cell signaling in cells bearing linker for activation of T-cell (LAT) molecules resistant to ubiquitylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis 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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Pooled it
- Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly.Cellular & molecular immunology · 2012Trial
- Low Levels of Mouse γδ T Cell Development Persist in the Presence of Null Mutants of the LAT Adaptor.International journal of molecular sciences · 2025Article
- Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.Nature cancer · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia.Cancer cell · 2025Article
- Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.Antioxidants (Basel, Switzerland) · 2024Article
- CD28 shapes T cell receptor signaling by regulating Lck dynamics and ZAP70 activation.Frontiers in immunology · 2024Article
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
- Article
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- RNA-electroporated T cells for cancer immunotherapy.Oncoimmunology · 2020Review
- LRCH1 deficiency enhances LAT signalosome formation and CD8Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction.International journal of molecular sciences · 2020Review
- Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation.Frontiers in cell and developmental biology · 2020Review
- Coordinating Cytoskeleton and Molecular Traffic in T Cell Migration, Activation, and Effector Functions.Frontiers in cell and developmental biology · 2020Review
- Bypassing ubiquitination enables LAT recycling to the cell surface and enhanced signaling in T cells.PloS one · 2020Article
- TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps.Nature communications · 2019Article
- Orchestration of Immunological Synapse Assembly by Vesicular Trafficking.Frontiers in cell and developmental biology · 2019Review
- ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters.Journal of cell science · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Linker for activation of T cells (LAT) plays a central role in T-cell activation by nucleating signaling complexes that are critical for the propagation of T-cell signals from the plasma membrane to the cellular interior. The role of phosphorylation and palmitoylation in LAT function has been well studied, but not much is known about other strategies by which the cell modulates LAT activity. We have focused on LAT ubiquitylation and have mapped the sites on which LAT is ubiquitylated. To elucidate the biological role of this process, we substituted LAT lysines with arginines. This resulted in a dramatic decrease in overall LAT ubiquitylation. Ubiquitylation-resistant mutants of LAT were internalized at rates comparable to wild-type LAT in a mechanism that required Cbl family proteins. However, these mutants displayed a defect in protein turnover rates. T-cell signaling was elevated in cells reconstituted with LAT mutants resistant to ubiquitylation, indicating that inhibition of LAT ubiquitylation enhances T-cell potency. These results support LAT ubiquitylation as a molecular checkpoint for attenuation 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.