ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 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
- THEMIS2 contributes to ovarian cancer metastasis via DOCK4-mediated activation of Rap1 signaling.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- 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
- Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation.Cellular and molecular life sciences : CMLS · 2024Article
- Themis controls T cell activation, effector functions, and metabolism of peripheral CD8Life science alliance · 2023Article
- Themis2 regulates natural killer cell memory function and formation.Nature communications · 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
- An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases.International journal of molecular sciences · 2022Review
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Key Vitamin D Target Genes with Functions in the Immune System.Nutrients · 2020Article
- Themis-associated phosphatase activity controls signaling in T cell development.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- THEMIS, the new kid on the block for T-cell development.Cellular & molecular immunology · 2017Article
- THEMIS: Two Models, Different Thresholds.Trends in immunology · 2017Review
- Thymic progenitors of TCRαβThe Journal of experimental medicine · 2017Article
- Proteomic Analysis of Regulatory T Cells Reveals the Importance of Themis1 in the Control of Their Suppressive Function.Molecular & cellular proteomics : MCP · 2017Article
- Themis2: setting the threshold for B-cell selection.Cellular & molecular immunology · 2017Article
- THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.Nature immunology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Themis1, a recently identified T cell protein, has a critical function in the generation of mature CD4(+)CD8(-) and CD4(-)CD8(+) (CD4 and CD8 single-positive [SP]) thymocytes and T cells. Although Themis1 has been shown to bind to the adaptor proteins LAT and Grb2, previous studies have yielded conflicting results regarding whether thymocytes from Themis1(-/-) mice exhibit TCR-mediated signaling defects. In this study, we demonstrate that, in the absence of Themis1, TCR-mediated signaling is selectively impaired in CD4 SP and CD8 SP thymocytes but is not affected in CD4(+)CD8(+) double-positive thymocytes despite high expression of Themis1 in double-positive thymocytes. Like Themis1, Themis2, a related member of the Themis family, which is expressed in B cells and macrophages, contains two conserved cysteine-based domains, a proline-rich region, and a nuclear localization signal. To determine whether Themis1 and Themis2 can perform similar functions in vivo, we analyzed T cell development and TCR-mediated signaling in Themis1(-/-) mice reconstituted with either Themis1 or Themis2 transgenes. Notably, Themis1 and Themis2 exhibited the same potential to restore T cell development and TCR-mediated signaling in Themis1(-/-) mice. Both proteins were tyrosine phosphorylated and were recruited within Grb2 signaling complexes to LAT following TCR engagement. These results suggest that conserved molecular features of the Themis1 and Themis2 proteins are important for their biological activity and predict that Themis1 and Themis2 may perform similar functions in T and B cells, respectively.
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