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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2012
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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. |
format | Online Article Text |
id | pubmed-3462612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
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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