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.
In: Biochemical Journal, Vol. 442, No. 3, 15.03.2012, p. 649-659.Research output: Contribution to journal › Article
}
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 -