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LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells

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 e...

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Autores principales: Tamás, Peter, Macintyre, Andrew, Finlay, David, Clarke, Rosemary, Feijoo-Carnero, Carmen, Ashworth, Alan, Cantrell, Doreen
Formato: Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988414/
https://www.ncbi.nlm.nih.gov/pubmed/19830737
http://dx.doi.org/10.1002/eji.200939677
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author Tamás, Peter
Macintyre, Andrew
Finlay, David
Clarke, Rosemary
Feijoo-Carnero, Carmen
Ashworth, Alan
Cantrell, Doreen
author_facet Tamás, Peter
Macintyre, Andrew
Finlay, David
Clarke, Rosemary
Feijoo-Carnero, Carmen
Ashworth, Alan
Cantrell, Doreen
author_sort Tamás, Peter
collection PubMed
description 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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spelling pubmed-29884142010-12-06 LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells Tamás, Peter Macintyre, Andrew Finlay, David Clarke, Rosemary Feijoo-Carnero, Carmen Ashworth, Alan Cantrell, Doreen Eur J Immunol Molecular Immunology 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. WILEY-VCH Verlag 2010-01 /pmc/articles/PMC2988414/ /pubmed/19830737 http://dx.doi.org/10.1002/eji.200939677 Text en Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Molecular Immunology
Tamás, Peter
Macintyre, Andrew
Finlay, David
Clarke, Rosemary
Feijoo-Carnero, Carmen
Ashworth, Alan
Cantrell, Doreen
LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title_full LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title_fullStr LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title_full_unstemmed LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title_short LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells
title_sort lkb1 is essential for the proliferation of t-cell progenitors and mature peripheral t cells
topic Molecular Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988414/
https://www.ncbi.nlm.nih.gov/pubmed/19830737
http://dx.doi.org/10.1002/eji.200939677
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