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Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells

PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antige...

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Autores principales: Navarro, Maria N., Sinclair, Linda V., Feijoo-Carnero, Carmen, Clarke, Rosemary, Matthews, Sharon A., Cantrell, Doreen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462612/
https://www.ncbi.nlm.nih.gov/pubmed/22233340
http://dx.doi.org/10.1042/BJ20111700
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author Navarro, Maria N.
Sinclair, Linda V.
Feijoo-Carnero, Carmen
Clarke, Rosemary
Matthews, Sharon A.
Cantrell, Doreen A.
author_facet Navarro, Maria N.
Sinclair, Linda V.
Feijoo-Carnero, Carmen
Clarke, Rosemary
Matthews, Sharon A.
Cantrell, Doreen A.
author_sort Navarro, Maria N.
collection PubMed
description PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antigens in the T-cells of PKD2-null mice or mice deficient in PKD2 catalytic activity. We also developed a single cell assay to quantify PKD2 activation as T-cells respond to developmental stimuli or engagement of α/β TCR complexes in vivo. Strikingly, PKD2 loss caused increases in thymic output, lymphadenopathy and splenomegaly in TCR transgenic mice. The precise magnitude and timing of PKD2 activation during T-cell development is thus critical to regulate thymic homoeostasis. PKD2-null T-cells that exit the thymus have a normal transcriptome, but show a limited and abnormal transcriptional response to antigen. Transcriptional profiling reveals the full consequences of PKD2 loss and maps in detail the selective, but critical, function for PKD2 in signalling by α/β mature TCR complexes in peripheral T-cells.
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spelling pubmed-34626122012-10-12 Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells Navarro, Maria N. Sinclair, Linda V. Feijoo-Carnero, Carmen Clarke, Rosemary Matthews, Sharon A. Cantrell, Doreen A. Biochem J Research Article PKD (protein kinase D) 2 is a serine/threonine kinase activated by diacylglycerol in response to engagement of antigen receptors in lymphocytes. To explore PKD2 regulation and function in TCR (T-cell antigen receptor) signal transduction we expressed TCR complexes with fixed affinity for self antigens in the T-cells of PKD2-null mice or mice deficient in PKD2 catalytic activity. We also developed a single cell assay to quantify PKD2 activation as T-cells respond to developmental stimuli or engagement of α/β TCR complexes in vivo. Strikingly, PKD2 loss caused increases in thymic output, lymphadenopathy and splenomegaly in TCR transgenic mice. The precise magnitude and timing of PKD2 activation during T-cell development is thus critical to regulate thymic homoeostasis. PKD2-null T-cells that exit the thymus have a normal transcriptome, but show a limited and abnormal transcriptional response to antigen. Transcriptional profiling reveals the full consequences of PKD2 loss and maps in detail the selective, but critical, function for PKD2 in signalling by α/β mature TCR complexes in peripheral T-cells. Portland Press Ltd. 2012-02-24 2012-03-15 /pmc/articles/PMC3462612/ /pubmed/22233340 http://dx.doi.org/10.1042/BJ20111700 Text en © 2012 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Navarro, Maria N.
Sinclair, Linda V.
Feijoo-Carnero, Carmen
Clarke, Rosemary
Matthews, Sharon A.
Cantrell, Doreen A.
Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title_full Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title_fullStr Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title_full_unstemmed Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title_short Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
title_sort protein kinase d2 has a restricted but critical role in t-cell antigen receptor signalling in mature t-cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462612/
https://www.ncbi.nlm.nih.gov/pubmed/22233340
http://dx.doi.org/10.1042/BJ20111700
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