PKC-θ exists in an oxidized inactive form in naive human T cells.

Autor: Essen, Marina Rode, Kongsbak, Martin, Levring, Trine Bøegh, Hansen, Ann Kathrine, Boding, Lasse, Lauritsen, Jens Peter Holst, Woetmann, Anders, Baier, Gottfried, Ødum, Niels, Bonefeld, Charlotte Menné, Geisler, Carsten
Zdroj: European Journal of Immunology; Jun2013, Vol. 43 Issue 6, p1659-1666, 8p
Abstrakt: 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 k Da 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index