TY - JOUR
T1 - PKC-θ exists in an oxidized inactive form in naive human T cells
AU - von Essen, Marina Rode
AU - Kongsbak, Martin
AU - Levring, Trine Bøegh
AU - Hansen, Ann Kathrine
AU - Boding, Lasse
AU - Lauritsen, Jens Peter Holst
AU - Woetmann, Anders
AU - Baier, Gottfried
AU - Odum, Niels
AU - Bonefeld, Charlotte Menné
AU - Geisler, Carsten
N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2013/6
Y1 - 2013/6
N2 - PKC-θ plays a central role in TCR-induced IL-2 production and T-cell proliferation. The aim of the present study was to analyse how PKC-θ is regulated in human T cells during T-cell activation and differentiation. We show that PKC-θ is found in a high-molecular disulfide-linked complex in naïve T cells, and that PKC-θ most likely is inactive in this form. In parallel with the accumulation of the major redox regulators, glutathione and thioredoxin, PKC-θ is gradually reduced to the 82 kDa active form during T-cell activation. We demonstrate that PKC-θ is recruited to the plasma membrane in the disulfide-linked form in naïve T cells, and that activation of PKC-θ is redox dependent and requires de novo synthesis of glutathione. This is the first study that shows that the activity of PKC-θ is regulated by the intracellular redox state, and that PKC-θ is recruited to the plasma membrane in an inactive form in naïve T cells. Our observations underscore the existence of major differences in TCR signaling in naïve versus primed T cells.
AB - PKC-θ plays a central role in TCR-induced IL-2 production and T-cell proliferation. The aim of the present study was to analyse how PKC-θ is regulated in human T cells during T-cell activation and differentiation. We show that PKC-θ is found in a high-molecular disulfide-linked complex in naïve T cells, and that PKC-θ most likely is inactive in this form. In parallel with the accumulation of the major redox regulators, glutathione and thioredoxin, PKC-θ is gradually reduced to the 82 kDa active form during T-cell activation. We demonstrate that PKC-θ is recruited to the plasma membrane in the disulfide-linked form in naïve T cells, and that activation of PKC-θ is redox dependent and requires de novo synthesis of glutathione. This is the first study that shows that the activity of PKC-θ is regulated by the intracellular redox state, and that PKC-θ is recruited to the plasma membrane in an inactive form in naïve T cells. Our observations underscore the existence of major differences in TCR signaling in naïve versus primed T cells.
U2 - 10.1002/eji.201243140
DO - 10.1002/eji.201243140
M3 - Journal article
C2 - 23436678
SN - 0014-2980
VL - 43
SP - 1659
EP - 1666
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -