ArticleScience signaling2013
The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Liquid-liquid phase separation drives immune signaling transduction in cancer: a bibliometric and visualized study from 1992 to 2024.Frontiers in oncology · 2025Pooled it
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Review
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 2026Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Heterogeneity of Signaling Complex Nanostructure in T Cells Activated Via the T Cell Antigen Receptor.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2023Article
- Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.Nature communications · 2022Article
- A two-component protein condensate of the EGFR cytoplasmic tail and Grb2 regulates Ras activation by SOS at the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Phase separation in immune signalling.Nature reviews. Immunology · 2022Review
- Systems-level conservation of the proximal TCR signaling network of mice and humans.The Journal of experimental medicine · 2022Article
- Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu.Journal of molecular cell biology · 2021Review
- Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch.Cell reports · 2021Article
- Coupled membrane lipid miscibility and phosphotyrosine-driven protein condensation phase transitions.Biophysical journal · 2021Article
- The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions.Cellular signalling · 2020Article
- Article
- The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell-specific adapter protein.The Journal of biological chemistry · 2019Article
- Regulation of Transmembrane Signaling by Phase Separation.Annual review of biophysics · 2019Review
- A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.Science (New York, N.Y.) · 2019Article
- Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events.Science signaling · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The activation of the small guanosine triphosphatase Ras by the guanine nucleotide exchange factor (GEF) Sos1 (Son of Sevenless 1) is a central feature of many receptor-stimulated signaling pathways. In developing T cells (thymocytes), Sos1-dependent activation of extracellular signal-regulated kinase (ERK) is required to stimulate cellular proliferation and differentiation. We showed that in addition to its GEF activity, Sos1 acted as a scaffold to nucleate oligomerization of the T cell adaptor protein LAT (linker for activation of T cells) in vivo. The scaffold function of Sos1 depended on its ability to bind to the adaptor protein Grb2. Furthermore, the GEF activity of Sos1 and the Sos1-dependent oligomerization of LAT were separable functions in vivo. Whereas the GEF activity of Sos1 was required for optimal ERK phosphorylation in response to T cell receptor (TCR) stimulation, the Sos1-dependent oligomerization of LAT was required for maximal TCR-dependent phosphorylation and activation of phospholipase C-γ1 and Ca(2+) signaling. Finally, both of these Sos1 functions were required for early thymocyte proliferation. Whereas transgenic restoration of either the GEF activity or the LAT oligomerization functions of Sos1 alone failed to rescue thymocyte development in Sos1-deficient mice, simultaneous reconstitution of these two signals in the same cell restored normal T cell development. This ability of Sos1 to act both as a RasGEF and as a scaffold to nucleate Grb2-dependent adaptor oligomerization may also occur in other Grb2-dependent pathways, such as those activated by growth factor receptors.
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