title: Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells.
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 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.
authors.affiliation: The College of Life Sciences, Division of Cell Signalling and Immunology, The University of Dundee, Scotland, UK.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Navarro
authors.forename: Linda V
authors.initials: LV
authors.lastname: Sinclair
authors.forename: Carmen
authors.initials: C
authors.lastname: Feijoo-Carnero
authors.forename: Rosemary
authors.initials: R
authors.lastname: Clarke
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Matthews
authors.forename: Doreen A
authors.initials: DA
authors.lastname: Cantrell
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D050396:TRPP Cation Channels