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Navarro, MN, Sinclair, LV, Feijoo-Carnero, C, Clarke, R, Matthews, SA and Cantrell, DA (2012) Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells. Biochem. J. 442:649-59
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.
Animals; Cell Differentiation; Mice; Mice, Transgenic; Receptors, Antigen, T-Cell/genetics; Receptors, Antigen, T-Cell/metabolism; Signal Transduction; T-Lymphocytes/cytology; T-Lymphocytes/immunology; TRPP Cation Channels/genetics; TRPP Cation Channels/metabolism
|Gene product||Qualifier||GO Term||Evidence Code||with/from||Aspect||Extension||Notes||Status|
|GO:0004672 : protein kinase activity||
Figure 1 shows that 'PKD2 regulates thymic output.'
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