ArticleNature immunology2018
Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT.
Article in Nature immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 177 citations in OpenAlex.
- G protein-coupled receptor kinase 3 regulates CCR7 signaling, trafficking, and T cell responses to CCL19 and CCL21.The Journal of biological chemistry · 2026Article
- Article
- Close Contacts Unlocked: Nanopore-Stabilized Microvilli Bypass T Cell Receptor-Ligand-Dependent T Cell Activation.ACS nano · 2026Article
- TRAIL splice variant TRAILshort disrupts T cell receptor signaling and promotes immune tolerance in vivo.The Journal of clinical investigation · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Weak SLP-76/PLC-γ1 interaction fine-tunes T cell receptor signal strength to optimize T cell responsiveness.Nature communications · 2026Article
- T cell engagers in autoimmune diseases.Nature reviews. Immunology · 2026Review
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- Palmitoylation-dependent regulation of innate and adaptive immunity: molecular insights and translational opportunities.Cellular & molecular biology letters · 2026Review
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- 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
- Development of αβ and γδ T Cells in the Thymus and Methods of Analysis.International journal of molecular sciences · 2025Review
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
- Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.bioRxiv : the preprint server for biology · 2025Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
T cell-antigen receptor (TCR) signaling requires the sequential activities of the kinases Lck and Zap70. Upon TCR stimulation, Lck phosphorylates the TCR, thus leading to the recruitment, phosphorylation, and activation of Zap70. Lck binds and stabilizes phosho-Zap70 by using its SH2 domain, and Zap70 phosphorylates the critical adaptors LAT and SLP76, which coordinate downstream signaling. It is unclear whether phosphorylation of these adaptors occurs through passive diffusion or active recruitment. We report the discovery of a conserved proline-rich motif in LAT that mediates efficient LAT phosphorylation. Lck associates with this motif via its SH3 domain, and with phospho-Zap70 via its SH2 domain, thereby acting as a molecular bridge that facilitates the colocalization of Zap70 and LAT. Elimination of this proline-rich motif compromises TCR signaling and T cell development. These results demonstrate the remarkable multifunctionality of Lck, wherein each of its domains has evolved to orchestrate a distinct step in TCR signaling.
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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.