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

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

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Original languageEnglish
Pages649-659
Number of pages11
JournalBiochemical Journal
Journal publication date15 Mar 2012
Journal number3
Volume442
Early online date10/01/12
DOIs
StatePublished

Abstract

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 a/ß 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 a/ß mature TCR complexes in peripheral T-cells. © The Authors Journal compilation © 2012 Biochemical Society.

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