ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Novel TCR-Mediated Mechanisms of Notch Activation and Signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Ciclopirox reprograms effector responses and modulates Notch1 activation in activated human T cells.iScience · 2026Article
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- Article
- Article
- Review
- Impact of the Multiple Sclerosis-Associated Genetic VariantNeurology(R) neuroimmunology & neuroinflammation · 2024Article
- A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function.Immunity · 2023Article
- Notch signaling pathway: a new target for neuropathic pain therapy.The journal of headache and pain · 2023Review
- Astrogliosis in multiple sclerosis and neuro-inflammation: what role for the notch pathway?Frontiers in immunology · 2023Review
- Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.Frontiers in immunology · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
- NOTCH1 Signalling: A key pathway for the development of high-risk chronic lymphocytic leukaemia.Frontiers in oncology · 2022Review
- Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses.Frontiers in immunology · 2022Article
- Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.The EMBO journal · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Notch receptor is an evolutionarily highly conserved transmembrane protein that is essential to a wide spectrum of cellular systems. Notch signaling is especially important to T cell development, and its deregulation leads to leukemia. Although not well characterized, it continues to play an integral role in peripheral T cells, in which a unique mode of Notch activation can occur. In contrast to canonical Notch activation initiated by adjacent ligand-expressing cells, TCR stimulation is sufficient to induce Notch signaling. However, the interactions between these two pathways have not been defined. In this article, we show that Notch activation occurs in peripheral T cells within a few hours post-TCR stimulation and is required for optimal T cell activation. Using a panel of inhibitors against components of the TCR signaling cascade, we demonstrate that Notch activation is facilitated through initiation of protein kinase C-induced ADAM activity. Moreover, our data suggest that internalization of Notch via endocytosis plays a role in this process. Although ligand-mediated Notch stimulation relies on mechanical pulling forces that disrupt the autoinhibitory domain of Notch, we hypothesized that, in T cells in the absence of ligands, these conformational changes are induced through chemical adjustments in the endosome, causing alleviation of autoinhibition and receptor activation. Thus, T cells may have evolved a unique method of Notch receptor activation, which is described for the first time, to our knowledge, in this article.
Indexed as
Identifiers
What OpenQuestion holds
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.