ArticleJournal of immunology (Baltimore, Md. : 1950)2013
GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- 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
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- ZDHHC21-driven S-palmitoylation of Themis regulates the function of T cells and maintains homeostatic balance.Cell communication and signaling : CCS · 2025Article
- THEMIS2 contributes to ovarian cancer metastasis via DOCK4-mediated activation of Rap1 signaling.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- T lymphocyte-specific deletion of SHP1 and SHP2 promotes activation-induced cell death of CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.Antioxidants (Basel, Switzerland) · 2024Article
- Inhibitory CARs fail to protect from immediate T cell cytotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Article
- 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
- Interrogating ligand-receptor interactions using highly sensitive cellular biosensors.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
- Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells.eLife · 2022Article
- NKG2A-checkpoint inhibition and its blockade critically depends on peptides presented by its ligand HLA-E.Immunology · 2022Article
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Protein ubiquitination in T cell development.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Thymocyte-expressed molecule involved in selection (THEMIS) is a recently identified regulator of thymocyte positive selection. THEMIS's mechanism of action is unknown, and whether it has a role in TCR-proximal signaling is controversial. In this article, we show that THEMIS and the adapter molecule growth factor receptor-bound protein 2 (GRB2) associate constitutively through binding of a conserved PxRPxK motif within the proline-rich region 1 of THEMIS to the C-terminal SH3-domain of GRB2. This association is indispensable for THEMIS recruitment to the immunological synapse via the transmembrane adapter linker for activation of T cells (LAT) and for THEMIS phosphorylation by Lck and ZAP-70. Two major sites of tyrosine phosphorylation were mapped to a YY-motif close to proline-rich region 1. The YY-motif was crucial for GRB2 binding, suggesting that this region of THEMIS might control local phosphorylation-dependent conformational changes important for THEMIS function. Finally, THEMIS binding to GRB2 was required for thymocyte development. Our data firmly assign THEMIS to the TCR-proximal signaling cascade as a participant in the LAT signalosome and suggest that the THEMIS-GRB2 complex might be involved in shaping the nature of Ras signaling, thereby governing thymic selection.
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Registered trials
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