ArticleThe Journal of experimental medicine2001
Knock-in mutation of the distal four tyrosines of linker for activation of T cells blocks murine T cell development.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 103 citations in OpenAlex.
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- 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
- Step-Wise Assembly of LAT Signaling Clusters Immediately After T Cell Receptor Triggering Contributes to Signal Propagation.International journal of molecular sciences · 2025Article
- Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.Antioxidants (Basel, Switzerland) · 2024Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- Title: Bioinformatic Identification of Genes Involved in Diabetic Nephropathy Fibrosis and their Clinical Relevance.Biochemical genetics · 2023Article
- Identification of useful biomolecular markers in kidney renal clear cell carcinoma: an in silico and in vitro analysis-based study.American journal of translational research · 2023Article
- Bioinformatics analysis of the key genes in osteosarcoma metastasis and immune invasion.Translational pediatrics · 2022Article
- Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.The Journal of international medical research · 2021Article
- A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling.Cells · 2021Article
- The Clinical Aspect of Adaptor Molecules in T Cell Signaling: Lessons Learnt From Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions.Cellular signalling · 2020Article
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
- A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.Frontiers in immunology · 2018Article
- Tonic Signals: Why Do Lymphocytes Bother?Trends in immunology · 2017Review
- Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in LAT.The Journal of experimental medicine · 2016Article
- The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters.The Journal of biological chemistry · 2015Review
- Identification of functional, short-lived isoform of linker for activation of T cells (LAT).Genes and immunity · 2014Article
- A phospholipase C-γ1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The integral membrane adapter protein linker for activation of T cells (LAT) performs a critical function in T cell antigen receptor (TCR) signal transduction by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT is tyrosine phosphorylated by ZAP-70 creating docking sites for multiple src homology 2-containing effector proteins. In the Jurkat T cell line, the distal four tyrosines of LAT bind PLCgamma-1, Grb2, and Gads. Mutation of these four tyrosine residues to phenylalanine (4YF) blocked TCR-mediated calcium mobilization, Erk activation, and nuclear factor (NF)-AT activation. In this study, we examined whether these four tyrosine residues were essential for T cell development by generating LAT "knock-in" mutant mice that express the 4YF mutant protein under the control of endogenous LAT regulatory sequences. Significantly, the phenotype of 4YF knock-in mice was identical to LAT(-/)- (null) mice; thymocyte development was arrested at the immature CD4(-)CD8(-) stage and no mature T cells were present. Knock-in mice expressing wild-type LAT protein, generated by a similar strategy, displayed a normal T cell developmental profile. These results demonstrate that the distal four tyrosine residues of LAT are essential for preTCR signaling and T cell development in vivo.
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