ArticleProceedings of the National Academy of Sciences of the United States of America2010
Grb2 functions at the top of the T-cell antigen receptor-induced tyrosine kinase cascade to control thymic selection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Characterization of a Cytokine-Independent STAT5 Activator.Biomedicines · 2026Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Systems and computational analysis of gene expression datasets reveals GRB-2 suppression as an acute immunomodulatory response against enteric infections in endemic settings.Frontiers in immunology · 2024Article
- GRB2 promotes thymocyte positive selection by facilitating THEMIS-mediated inactivation of SHP1.The Journal of experimental medicine · 2023Article
- GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production.Scientific reports · 2023Article
- Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.Frontiers in immunology · 2023Article
- Genetic association and single-cell transcriptome analyses reveal distinct features connecting autoimmunity with cancers.iScience · 2022Article
- Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2021Review
- LRCH1 deficiency enhances LAT signalosome formation and CD8Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.Science signaling · 2019Article
- Neddylation: a novel modulator of the tumor microenvironment.Molecular cancer · 2019Review
- Multi-omics integration reveals molecular networks and regulators of psoriasis.BMC systems biology · 2019Article
- T cell receptor signaling for γδT cell development.Inflammation and regeneration · 2019Review
- Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism.The Journal of infectious diseases · 2017Article
- THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.Nature immunology · 2017Article
- Optimization of methods for the genetic modification of human T cells.Immunology and cell biology · 2015Article
- The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters.The Journal of biological chemistry · 2015Review
- Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation.PLoS pathogens · 2015Article
- THEMIS is required for pathogenesis of cerebral malaria and protection against pulmonary tuberculosis.Infection and immunity · 2015Article
- Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.PloS one · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Grb2 is an adaptor molecule that mediates Ras-MAPK activation induced by various receptors. Here we show that conditional ablation of Grb2 in thymocytes severely impairs both thymic positive and negative selections. Strikingly, the mutation attenuates T-cell antigen receptor (TCR) proximal signaling, including tyrosine phosphorylation of multiple signaling proteins and Ca(2+) influx. The defective TCR signaling can be attributed to a marked impairment in Lck activation. Ectopic expression of a mutant Grb2 composed of the central SH2 and the C-terminal SH3 domains in Grb2(-/-) thymocytes fully restores thymocyte development. Thus, Grb2 plays a pivotal role in both thymic positive and negative selection. It amplifies TCR signaling at the top end of the tyrosine phosphorylation cascade via a scaffolding function.
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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.