ArticleProceedings of the National Academy of Sciences of the United States of America2015
Dynamin 2-dependent endocytosis sustains T-cell receptor signaling and drives metabolic reprogramming in T lymphocytes.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Targeting mTOR in Systemic Lupus Erythematosus: From Immune Cell Dysfunction to Clinical Translation.Journal of inflammation research · 2026Review
- Integrin linked kinase and threonine tyrosine kinase modulate TCR signaling.Scientific reports · 2025Article
- Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles activate CD4+ T cells from Chagas cardiomyopathy patients and are associated with ventricular dysfunction.Frontiers in immunology · 2025Article
- NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.Cellular and molecular life sciences : CMLS · 2024Article
- GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.Nature communications · 2024Article
- Dynamin 2-mediated endocytosis of BLT1 is required for IL-8 production in HMC-1 cells induced by Trichomonas vaginalis-derived secretory products.Parasites, hosts and diseases · 2024Article
- Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation.Nature communications · 2024Article
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity.Journal of experimental & clinical cancer research : CR · 2023Review
- Article
- Optical sensing and control of T cell signaling pathways.Frontiers in physiology · 2023Review
- Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022Review
- The role of endocytic trafficking in antigen T cell receptor activation.Biomedical journal · 2022Review
- Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum.The Journal of cell biology · 2021Article
- Mechanisms and functions of endocytosis in T cells.Cell communication and signaling : CCS · 2021Review
- Europium sulfide nanoprobes predict antiretroviral drug delivery into HIV-1 cell and tissue reservoirs.Nanotheranostics · 2021Article
- T cell receptor signaling defines the fate and pathway of ICOS internalization.Biochemistry and biophysics reports · 2020Article
- IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses.Nature communications · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Prolonged T-cell receptor (TCR) signaling is required for the proliferation of T lymphocytes. Ligation of the TCR activates signaling, but also causes internalization of the TCR from the cell surface. How TCR signaling is sustained for many hours despite lower surface expression is unknown. Using genetic inhibition of endocytosis, we show here that TCR internalization promotes continued TCR signaling and T-lymphocyte proliferation. T-cell-specific deletion of dynamin 2, an essential component of endocytosis, resulted in reduced TCR signaling strength, impaired homeostatic proliferation, and the inability to undergo clonal expansion in vivo. Blocking endocytosis resulted in a failure to maintain mammalian target of rapamycin (mTOR) activity and to stably induce the transcription factor myelocytomatosis oncogene (c-Myc), which led to metabolic stress and a defect in cell growth. Our results support the concept that the TCR can continue to signal after it is internalized from the cell surface, thereby enabling sustained signaling and cell proliferation.
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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.