ArticlePloS one2011
The transmembrane adaptor protein SIT inhibits TCR-mediated signaling.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Pooled it
- Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.British journal of cancer · 2026Article
- Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.Molecular neurobiology · 2025Article
- SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients.Immunologic research · 2024Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Comprehensive immune profiling reveals thatFrontiers in immunology · 2023Article
- Discovery and Validation of a SIT1-Related Prognostic Signature Associated with Immune Infiltration in Cutaneous Melanoma.Journal of personalized medicine · 2022Article
- Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.American journal of respiratory cell and molecular biology · 2022Article
- Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19.Human genetics · 2021Article
- PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4Frontiers in immunology · 2021Article
- Bioinformatics analysis to screen key prognostic genes in the breast cancer tumor microenvironment.Bioengineered · 2020Article
- The effects of short-term high-fat feeding on exercise capacity: multi-tissue transcriptome changes by RNA sequencing analysis.Lipids in health and disease · 2017Article
- Inappropriate costimulation and aberrant DNA methylation as therapeutic targets in angioimmunoblastic T-cell lymphoma.Biomarker research · 2017Article
- Innate memory T cells.Advances in immunology · 2015Review
- TCR activation kinetics and feedback regulation in primary human T cells.Cell communication and signaling : CCS · 2013Article
- Systemic steroid exposure is associated with differential methylation in chronic obstructive pulmonary disease.American journal of respiratory and critical care medicine · 2012Article
- TCR-mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells.EMBO reports · 2012Article
- Immune system modulation by low-dose ionizing radiation-induced adaptive response.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transmembrane adaptor proteins (TRAPs) organize signaling complexes at the plasma membrane, and thus function as critical linkers and integrators of signaling cascades downstream of antigen receptors. We have previously shown that the transmembrane adaptor protein SIT regulates the threshold for thymocyte selection. Moreover, T cells from SIT-deficient mice are hyperresponsive to CD3 stimulation and undergo enhanced lymphopenia-induced homeostatic proliferation, thus indicating that SIT inhibits TCR-mediated signaling. Here, we have further addressed how SIT regulates signaling cascades in T cells. We demonstrate that the loss of SIT enhances TCR-mediated Akt activation and increased phosphorylation/inactivation of Foxo1, a transcription factor of the Forkhead family that inhibits cell cycle progression and regulates T-cell homeostasis. We have also shown that CD4(+) T cells from SIT-deficient mice display increased CD69 and CD40L expression indicating an altered activation status. Additional biochemical analyses further revealed that suppression of SIT expression by RNAi in human T cells resulted in an enhanced proximal TCR signaling. In summary, the data identify SIT as an important modulator of TCR-mediated signaling that regulates T-cell activation, homeostasis and tolerance.
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Registered trials
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.