LKB1 is essential for the proliferation of T‐cell progenitors and mature peripheral T cells
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The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co‐ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differentiation to ensure that they can meet the energy requirements for development. The present study explores the role of LKB1 in this process and shows that loss of LKB1 prevents thymocyte differentiation and the production of peripheral T lymphocytes. We find that LKB1 is required for several key metabolic processes in T‐cell progenitors. For example, LKB1 controls expression of CD98, a key subunit of the L ‐system aa transporter and is also required for the pre‐TCR to induce and sustain the regulated phosphorylation of the ribosomal S6 subunit, a key regulator of protein synthesis. In the absence of LKB1 TCR‐β‐selected thymocytes failed to proliferate and did not survive. LBK1 was also required for survival and proliferation of peripheral T cells. These data thus reveal a conserved and essential role for LKB1 in the proliferative responses of both thymocytes and mature T cells.
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Loss of LKB1-AMPK signaling promotes increased mTORC1 activity in both naïve and TEFF cells, which in turn facilitates production of the TH1 cytokine interferon-γ (IFN-γ) by TEFF cells.
“Loss of LKB1-AMPK signaling promotes increased mTORC1 activity in both naïve and TEFF cells (88, 90), which in turn facilitates production of the TH1 cytokine interferon-γ (IFN-γ) by TEFF cells (88).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [90]
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- Authors
- Tamás, P., Macintyre, A., Finlay, D., Clarke, R., Feijoo‐Carnero, C., Ashworth, A., & Cantrell, D.
- Affiliations
- University of Dundee (GB)
- Institute of Cancer Research (GB)
- Corresponding author
- Cantrell, Doreen
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2009-12-30
- Volume
- 40
- Issue
- 1
- Pages
- 242-253
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- PMC
- PMC2988414
- OpenAlex
- W2167539814
- Cited by
- 94
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 3 · 2015: 6 · 2014: 11 · 2013: 7 · 2012: 8
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (acceptedVersion, other-oa)
- Funders
- Wellcome Trust (GR065975, 065975)
- Cancer Research UK (A8363)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- LKB1, T cell development, thymocyte proliferation, thymocyte differentiation, T cell metabolism, CD98, amino acid transporters, protein synthesis, pre-TCR signaling, T cell survival, peripheral T cells
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Mice, Inbred C57BL, T-Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, Protein Serine-Threonine Kinases, Fusion Regulatory Protein-1, Cell Proliferation, Mice, Precursor Cells, T-Lymphoid, AMP-Activated Protein Kinases
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