TY  - JOUR
T1  - Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
A1  - Navarro,Maria N.
A1  - Sinclair,Linda V.
A1  - Feijoo-Carnero,Carmen
A1  - Clarke,Rosemary
A1  - Matthews,Sharon A.
A1  - Cantrell,Doreen A.
AU  - Navarro,Maria N.
AU  - Sinclair,Linda V.
AU  - Feijoo-Carnero,Carmen
AU  - Clarke,Rosemary
AU  - Matthews,Sharon A.
AU  - Cantrell,Doreen A.
PY  - 2012/3/15
Y1  - 2012/3/15
N2  - 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.
AB  - 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.
KW  - Cytokine
KW  - Lymphocyte
KW  - Pre-cell antigen receptor
KW  - Protein kinase D (PKD)
KW  - T-cell antigen receptor (TCR)
KW  - Thymus
UR  - http://ukpmc.ac.uk/abstract/MED/22233340
U2  - 10.1042/BJ20111700
DO  - 10.1042/BJ20111700
M1  - Article
JO  - Biochemical Journal
JF  - Biochemical Journal
SN  - 0264-6021
IS  - 3
VL  - 442
SP  - 649
EP  - 659
ER  -