ArticleEuropean journal of immunology2008
The role of the PI3K-AKT kinase pathway in T-cell development beyond the beta checkpoint.
Article in European journal of immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
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- MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia.Cancer reports (Hoboken, N.J.) · 2023Article
- Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF.Nature immunology · 2023Article
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- Post-Irradiation Thymic Regeneration in B6C3F1 Mice Is Age Dependent and Modulated by Activation of the PI3K-AKT-mTOR Pathway.Biology · 2022Article
- Trends in TREC values according to age and gender in Chinese children and their clinical applications.European journal of pediatrics · 2022Article
- Calcium Signaling Is Impaired in PTEN-Deficient T Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Article
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- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology.Frontiers in endocrinology · 2020Review
- RRAS2 shapes the TCR repertoire by setting the threshold for negative selection.The Journal of experimental medicine · 2019Article
- Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression ofDevelopment (Cambridge, England) · 2018Article
- Therapeutic Options for Aggressive T-Cell Lymphomas.Current hematologic malignancy reports · 2017Review
- Simian varicella virus causes robust transcriptional changes in T cells that support viral replication.Virus research · 2017Article
- Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4American journal of respiratory cell and molecular biology · 2017Article
- Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Synergistic effects of interleukin-7 and pre-T cell receptor signaling in human T cell development.The Journal of biological chemistry · 2012Article
- Molecular mechanisms of (R,R)ZX-5 on NO synthesis and its anti-angiogenic effect.International journal of molecular sciences · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The PI3K-AKT pathway can mediate diverse biological responses and is crucial for optimal immune responses and lymphocyte development. Deletion of PI3K subunits or AKT leads to blockage of T-cell development at the TCR-beta checkpoint. Studies with over-expression of constitutively activated AKT have implicated this pathway in anti-apoptosis of developing thymocytes and in development of regulatory T cells. However, the role of endogenous PI3K-AKT in T-cell development beyond the TCR-beta checkpoint remains unclear. Here, we inhibited the endogenous PI3K-AKT pathway in thymocytes after double negative stages by expressing the negative regulator, PTEN. These mice exhibit normal early T-cell development, but the transition from intermediate single positive to double positive (DP) thymocytes is inhibited, leading to a significantly decreased number of DP, single positive thymocytes and peripheral T cells. Proliferation of peripheral T cells is reduced but apoptosis of DP cells and subsequent T-cell maturation, including regulatory T cells, are normal. AKT phosphorylation can be readily observed in most WT T-cell compartments but not DP thymocytes in response to TCR activation. Thus, the PI3K-AKT pathway is crucial for the transition of intermediate single positive to DP thymocytes but is dispensable for apoptosis and maturation of developing thymocytes.
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Registered trials
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