ArticleThe Journal of biological chemistry2011
T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 79 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
- Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) for Quantitative Proteomics.Advances in experimental medicine and biology · 2026Review
- ZDHHC21-driven S-palmitoylation of Themis regulates the function of T cells and maintains homeostatic balance.Cell communication and signaling : CCS · 2025Article
- Mutation of conserved MHC class I cytoplasmic tyrosine affects CD8+ T cell priming, effector function, and memory response.Frontiers in immunology · 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 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
- 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
- SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity.Nature communications · 2021Article
- Quantitative Interactomics of Lck-TurboID in Living Human T Cells Unveils T Cell Receptor Stimulation-Induced Proximal Lck Interactors.Journal of proteome research · 2021Article
- LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions.Molecular systems biology · 2020Article
- Spatiotemporal Regulation of Signaling: Focus on T Cell Activation and the Immunological Synapse.International journal of molecular sciences · 2020Review
- T cell receptor and cytokine signal integration in CD8Nature immunology · 2020Article
- Two gene set variation indexes as potential diagnostic tool for sepsis.American journal of translational research · 2020Article
- A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation.Frontiers in immunology · 2019Article
- HTLV-1 HBZ Protein Resides Exclusively in the Cytoplasm of Infected Cells in Asymptomatic Carriers and HAM/TSP Patients.Frontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Stimulation of the T cell antigen receptor (TCR) induces formation of a phosphorylation-dependent signaling network via multiprotein complexes, whose compositions and dynamics are incompletely understood. Using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics, we investigated the kinetics of signal propagation after TCR-induced protein tyrosine phosphorylation. We confidently assigned 77 proteins (of 758 identified) as a direct or indirect consequence of tyrosine phosphorylation that proceeds in successive "signaling waves" revealing the temporal pace at which tyrosine kinases activate cellular functions. The first wave includes thymocyte-expressed molecule involved in selection (THEMIS), a protein recently implicated in thymocyte development but whose signaling role is unclear. We found that tyrosine phosphorylation of THEMIS depends on the presence of the scaffold proteins Linker for activation of T cells (LAT) and SH2 domain-containing lymphocyte protein of 76 kDa (SLP-76). THEMIS associates with LAT, presumably via the adapter growth factor receptor-bound protein 2 (Grb2) and with phospholipase Cγ1 (PLC-γ1). RNAi-mediated THEMIS knock-down inhibited TCR-induced IL-2 gene expression due to reduced ERK and nuclear factor of activated T cells (NFAT)/activator protein 1 (AP-1) signaling, whereas JNK, p38, or nuclear factor κB (NF-κB) activation were unaffected. Our study reveals the dynamics of TCR-dependent signaling networks and suggests a specific role for THEMIS in early TCR signalosome 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.