ArticleThe Biochemical journal2001
Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells.Journal of leukocyte biology · 2015Trial
- Article
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 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
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T-Cell Adaptor Gads.European journal of immunology · 2025Article
- Analyzing Point Accumulation in Nanoscale Topography (PAINT) Data to Decipher T Cell Receptor Cluster Signalling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The LAT Rheostat as a Regulator of Megakaryocyte Activation.Thrombosis and haemostasis · 2024Article
- Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.The Journal of allergy and clinical immunology · 2024Article
- Ubiquitination of Immune System and Cancer Therapy.Advances in experimental medicine and biology · 2024Review
- 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
- GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production.Scientific reports · 2023Article
- Article
- Identification of GC-rich LAT genes in birds.PloS one · 2023Article
- Optical sensing and control of T cell signaling pathways.Frontiers in physiology · 2023Review
- SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR-T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells.Journal of proteome research · 2022Article
- T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.Frontiers in immunology · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell-receptor (TCR)-mediated LAT (linker for activation of T cells) phosphorylation is critical for the membrane recruitment of signalling complexes required for T-cell activation. Although tyrosine phosphorylation of LAT is required for recruitment and activation of signalling proteins, the molecular mechanism associated with this event is unclear. In the present study we reconstituted the LAT signalling pathway by demonstrating that a direct tyrosine phosphorylation of LAT with activated protein-tyrosine kinase Zap70 is necessary and sufficient for the association and activation of signalling proteins. Zap-70 efficiently phosphorylates LAT on tyrosine residues at positions 226, 191, 171, 132 and 127. By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively. Furthermore, by expression of LAT mutants in LAT-deficient T cells, we demonstrate that Tyr(191) and Tyr(171) are required for T-cell activation and Tyr(132) is required for the activation of PLCgamma1 and Ras signalling pathways.
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