ArticleThe Journal of experimental medicine2008
An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Unraveling CD4Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- TCRζ-driven pre-signaling organization of Lck in Rab11⁺ endosomes shapes TCR activation.Cellular & molecular biology letters · 2026Article
- Spatial regulation of Lck activation at the CD8 immune synapse revealed by a FRET-Based biosensor.Cellular and molecular life sciences : CMLS · 2026Article
- Pulmonary organoid models demonstrate compositionally driven epithelial plasticity and immune polarization.iScience · 2026Article
- Immune landscape of neoadjuvant chemoradiotherapy: involvement of MAL, a T-cell differentiation protein.Oncology research · 2025Article
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- The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers.Cancers · 2023Review
- Directed growth and fusion of membrane-wall microdomains requires CASP-mediated inhibition and displacement of secretory foci.Nature communications · 2023Article
- Rapid increase in transferrin receptor recycling promotes adhesion during T cell activation.BMC biology · 2022Article
- MALL, a membrane-tetra-spanning proteolipid overexpressed in cancer, is present in membraneless nuclear biomolecular condensates.Cellular and molecular life sciences : CMLS · 2022Article
- CNS endothelial derived extracellular vesicles are biomarkers of active disease in multiple sclerosis.Fluids and barriers of the CNS · 2022Article
- Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells.Cellular and molecular life sciences : CMLS · 2022Article
- Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.Frontiers in immunology · 2022Article
- Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.Scientific reports · 2021Article
- The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer.Cells · 2021Review
- Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein.European journal of immunology · 2021Article
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- Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse.International journal of molecular sciences · 2020Review
- A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.
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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.