ArticleJournal of immunology (Baltimore, Md. : 1950)2013
A phospholipase C-γ1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance.Cell reports. Medicine · 2023Article
- Adapting T Cell Receptor Ligand Discrimination CapabilityFrontiers in immunology · 2021Review
- Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.Nature immunology · 2019Article
- Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT.Nature immunology · 2018Article
- Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.Cancer immunology, immunotherapy : CII · 2018Article
- Review
- Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.PloS one · 2015Article
- Integrative biology of T cell activation.Nature immunology · 2014Review
- Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes.Cellular signalling · 2014Article
- Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling.Nature immunology · 2014Article
- Article
- Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells.Trends in immunology · 2013Review
- miRNA signature of mouse helper T cell hyper-proliferation.PloS one · 2013Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Mice expressing a germline mutation in the phospholipase C-γ1-binding site of linker for activation of T cells (LAT) show progressive lymphoproliferation and ultimately die at 4-6 mo age. The hyperactivated T cells in these mice show defective TCR-induced calcium flux but enhanced Ras/ERK activation, which is critical for disease progression. Despite the loss of LAT-dependent phospholipase C-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major Ras guanine exchange factor responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4(+) T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, protein kinase C-θ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting.
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