ArticleProceedings of the National Academy of Sciences of the United States of America2009
Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 71 citations in OpenAlex.
- Themis orchestrates T-cell development through coordinated regulation of mitochondrial metabolism and Jun family transcription factors.Chinese medical journal · 2026Article
- Structural and Biochemical Analysis of the CABIT1 Domain of THEMIS.bioRxiv : the preprint server for biology · 2026Article
- Structural and mechanistic insights into the constitutive Themis-Grb2 complex in T cell signalling.Nature communications · 2026Article
- The role of Themis in development of type 2 diabetes.Research square · 2025Article
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- THEMIS is a substrate and allosteric activator of SHP1, playing dual roles during T cell development.Nature structural & molecular biology · 2024Article
- Themis controls T cell activation, effector functions, and metabolism of peripheral CD8Life science alliance · 2023Article
- A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection.iScience · 2023Article
- GRB2 promotes thymocyte positive selection by facilitating THEMIS-mediated inactivation of SHP1.The Journal of experimental medicine · 2023Article
- THEMIS increases TCR signaling in CD4Science signaling · 2023Article
- Themis suppresses the effector function of CD8Cellular & molecular immunology · 2023Article
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Themis regulates metabolic signaling and effector functions in CD4Cellular & molecular immunology · 2021Article
- T cell self-reactivity during thymic development dictates the timing of positive selection.eLife · 2021Article
- T cell receptor and cytokine signal integration in CD8Nature immunology · 2020Article
- T cell receptor signaling for γδT cell development.Inflammation and regeneration · 2019Review
- Themis-associated phosphatase activity controls signaling in T cell development.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulatory mechanisms in T cell receptor signalling.Nature reviews. Immunology · 2018Review
- THEMIS: Two Models, Different Thresholds.Trends in immunology · 2017Review
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both CD4 and CD8 single positive cells in the thymus was severely inhibited, whereas all other TCR-induced events such as beta-selection, negative selection, peripheral activation, and homeostatic proliferation were unaffected. We found that Gasp constitutively associates with Grb2 via its N-terminal Src homology 3 domain, suggesting that Gasp acts as a thymocyte-specific adaptor for Grb2 or regulates Ras signaling in DP thymocytes. Collectively, we have described a gene called Gasp that is critical for positive selection.
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