ArticleMolecular and cellular biology2012
Deconstructing Ras signaling in the thymus.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- RasGRP1 signaling is required for Vγ2+ thymocyte c-Maf expression and γδT17 lineage programming.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Cutting Edge: Induced Loss of Rasgrp1 in Peripheral CD4+ T Cells of Conditional Rasgrp1-Deficient Mice Reveals an Essential Role for Rasgrp1 in TCR/CD28-Induced Ras-MAPK Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Case report: The cardio-facio-cutaneous syndrome due to a novel germline mutation inFrontiers in pediatrics · 2022Article
- Article
- Review
- Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.European journal of immunology · 2020Article
- Efficient CD4Cre-Mediated Conditional KRas Expression in Alveolar Macrophages and Alveolar Epithelial Cells Causes Fatal Hyperproliferative Pneumonitis.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Oncogenic RAS isoforms show a hierarchical requirement for the guanine nucleotide exchange factor SOS2 to mediate cell transformation.Science signaling · 2018Article
- Thymic progenitors of TCRαβThe Journal of experimental medicine · 2017Article
- Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1.The Journal of experimental medicine · 2017Article
- Sos1 disruption impairs cellular proliferation and viability through an increase in mitochondrial oxidative stress in primary MEFs.Oncogene · 2016Article
- The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters.The Journal of biological chemistry · 2015Review
- Enhanced T-cell activation and differentiation in lymphocytes from transgenic mice expressing ubiquitination-resistant 2KR LAT molecules.Gene therapy · 2015Article
- Absence of both Sos-1 and Sos-2 in peripheral CD4(+) T cells leads to PI3K pathway activation and defects in migration.European journal of immunology · 2015Article
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- CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.Cell death & disease · 2014Article
- Article
Corrections and comments
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Authors and funding
8 authors.
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Abstract
Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1 deletion was required to block negative selection. This functional redundancy in RasGEFs during negative selection may act as a failsafe mechanism ensuring appropriate central tolerance.
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Registered trials
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