ArticleProceedings of the National Academy of Sciences of the United States of America2015
Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- DHHC21 is a STIM1 protein S-acyltransferase that modulates immune function in vivo.Journal of cell science · 2026Article
- Palmitoylation-dependent regulation of innate and adaptive immunity: molecular insights and translational opportunities.Cellular & molecular biology letters · 2026Review
- DHHC21 is a STIM1 protein S-acyltransferase that modulates immune functionbioRxiv : the preprint server for biology · 2025Article
- ZDHHC21-driven S-palmitoylation of Themis regulates the function of T cells and maintains homeostatic balance.Cell communication and signaling : CCS · 2025Article
- S-palmitoylation of c-MET by CK2α-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity.Neuro-oncology · 2025Article
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.Life science alliance · 2025Article
- S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.Journal of Cancer · 2025Review
- Recruitment, regulation, and release: Control of signaling enzyme localization and function by reversible S-acylation.The Journal of biological chemistry · 2024Review
- Leveraging altered lipid metabolism in treating B cell malignancies.Progress in lipid research · 2024Review
- zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function.Acta pharmacologica Sinica · 2024Article
- A palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis.Nature cell biology · 2024Article
- ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma.Cell communication and signaling : CCS · 2024Article
- Metabolic transitions regulate global protein fatty acylation.The Journal of biological chemistry · 2024Article
- Protein S-palmitoylation modification: implications in tumor and tumor immune microenvironment.Frontiers in immunology · 2024Review
- Functions and mechanisms of the GPCR adaptor protein Norbin.Biochemical Society transactions · 2023Review
- Regulation of membrane protein structure and function by their lipid nano-environment.Nature reviews. Molecular cell biology · 2023Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- The Re-Localization of Proteins to or Away from Membranes as an Effective Strategy for Regulating Stress Tolerance in Plants.Membranes · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck. Lck palmitoylation kinetics are consistent with the activation of downstream signaling proteins, such as Zap70 and PLC-γ1. Inhibiting Lck palmitoylation not only disrupts proximal Fas signaling events, but also renders cells resistant to Fas-mediated apoptosis. Knockdown of the palmitoyl acyl transferase DHHC21 eliminates activation of Lck and downstream signaling after Fas receptor stimulation. Our findings demonstrate highly dynamic Lck palmitoylation kinetics that are essential for signaling downstream of the Fas receptor.
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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.