ArticleThe Biochemical journal2003
Selective interaction of LAT (linker of activated T cells) with the open-active form of Lck in lipid rafts reveals a new mechanism for the regulation of Lck in T cells.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- 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
- A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling.Cells · 2021Article
- Quantitative Interactomics of Lck-TurboID in Living Human T Cells Unveils T Cell Receptor Stimulation-Induced Proximal Lck Interactors.Journal of proteome research · 2021Article
- 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
- Distinct Mechanisms Regulate Lck Spatial Organization in Activated T Cells.Frontiers in immunology · 2016Article
- The role of tyrosine kinases in systemic lupus erythematosus and their potential as therapeutic targets.Expert review of clinical immunology · 2014Review
- Dynamic palmitoylation and the role of DHHC proteins in T cell activation and anergy.Advances in immunology · 2011Review
- T cell receptor signal initiation induced by low-grade stimulation requires the cooperation of LAT in human T cells.PloS one · 2010Article
- Constitutively active Lck kinase in T cells drives antigen receptor signal transduction.Immunity · 2010Article
- Lipid rafts and T-lymphocyte function: implications for autoimmunity.FEBS letters · 2008Review
- Lipid rafts in T cell signalling and disease.Seminars in cell & developmental biology · 2007Review
- Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Regulation of T-cell receptor signalling by membrane microdomains.Immunology · 2004Review
- Review
- Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus.The Journal of clinical investigation · 2004Article
- Lipid rafts in T cell receptor signalling .Molecular membrane biologyReview
- Regulation of expression and function of Lck tyrosine kinase by high cell density.Molecular membrane biologyArticle
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1 author at 1 institution in 1 country.
Funding
Abstract
In T cells, the lipid raft-associated Lck is strongly tyrosine phosphorylated and has reduced enzymic activity in contrast with the detergent-soluble pool, which has substantial activity. Lck tagged at the C-terminus (Lck/V5-His) was efficiently captured by epitope-specific reagents from the detergent-soluble fraction but not from lipid rafts. Binding was restored following urea denaturation, suggesting that Lck/V5-His is in a 'closed' conformation in these domains. In agreement with this hypothesis, the Tyr(505) --> Phe/V5-His and Arg(154) --> Lys/V5-His mutants, which disrupt the SH2-Tyr(505) intramolecular interaction, were efficiently precipitated from lipid rafts. In contrast to Lck, Fyn/V5-His was precipitated equally well from both fractions. In the LAT(linker of activated T cells)-deficient J.CaM2 cells, Tyr(505) phosphorylation of raft-associated Lck was reduced whereas its enzymic activity was elevated. This correlated with decreased levels of raft-localized Csk (C-terminal Src kinase) kinase. Increased tyrosine phosphorylation of Lck was restored in LAT-reconstituted J.CaM2 cells suggesting that LAT negatively regulates Lck activity in lipid rafts. Co-immunoprecipitation experiments from Tyr(505) --> Phe/V5-His-expressing cells revealed that LAT preferentially interacts with the 'open' form of Lck in T cell raft domains. These results demonstrate that, unlike the non-raft pool, Lck in lipid rafts has a 'closed'-inactive structure, and that LAT plays a role in maintaining this conformation, possibly by facilitating critical associations within lipid rafts via its capacity to interact with the 'open' form of the kinase.
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