ArticleeLife2016
Non-canonical antagonism of PI3K by the kinase Itpkb delays thymocyte β-selection and renders it Notch-dependent.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.International journal of molecular sciences · 2023Pooled it
- Liquid Biopsy in Hematologic Malignancies: Advances, Challenges, and Future Directions.Asia-Pacific journal of clinical oncology · 2026Review
- Construction of a treatment response prediction model for multiple myeloma based on multi-omics and machine learning.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Molecular targets of glucocorticoids that elucidate their therapeutic efficacy in aggressive lymphomas.Cancer cell · 2024Article
- Evidence that inositol 1,4,5-trisphosphate 3-kinase and inositol 1,3,4,5-tetrakisphosphate are negative regulators of platelet function.Research and practice in thrombosis and haemostasis · 2024Article
- Differential CpG DNA methylation of peripheral B cells, CD4Arthritis research & therapy · 2023Article
- Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage.Life science alliance · 2022Article
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Review
- Genomic Landscape of Hodgkin Lymphoma.Cancers · 2021Review
- Genetic Landscape of Relapsed and Refractory Diffuse Large B-Cell Lymphoma: A Systemic Review and Association Analysis With Next-Generation Sequencing.Frontiers in genetics · 2021Article
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Article
- Regulation of Hematopoietic Cell Development and Function Through Phosphoinositides.Frontiers in immunology · 2018Review
- Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.Chemical senses · 2017Review
- Comparative transcriptomes of adenocarcinomas and squamous cell carcinomas reveal molecular similarities that span classical anatomic boundaries.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
β-selection is the most pivotal event determining αβ T cell fate. Here, surface-expression of a pre-T cell receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. Besides the pre-TCR, β-selection also requires co-stimulatory signals from Notch receptors - key cell fate determinants in eukaryotes. Here, we show that this Notch-dependence is established through antagonistic signaling by the pre-TCR/Notch effector, phosphoinositide 3-kinase (PI3K), and by inositol-trisphosphate 3-kinase B (Itpkb). Canonically, PI3K is counteracted by the lipid-phosphatases Pten and Inpp5d/SHIP-1. In contrast, Itpkb dampens pre-TCR induced PI3K/Akt signaling by producing IP4, a soluble antagonist of the Akt-activating PI3K-product PIP3. Itpkb(-/-) thymocytes are pre-TCR hyperresponsive, hyperactivate Akt, downstream mTOR and metabolism, undergo an accelerated β-selection and can develop to CD4(+)CD8(+) cells without Notch. This is reversed by inhibition of Akt, mTOR or glucose metabolism. Thus, non-canonical PI3K-antagonism by Itpkb restricts pre-TCR induced metabolic activation to enforce coincidence-detection of pre-TCR expression and Notch-engagement.
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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.