title: PKC-θ exists in an oxidized inactive form in naive human T cells.
abstract: 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.
authors: Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Marina Rode
authors: MR
authors: von Essen
authors: Martin
authors: M
authors: Kongsbak
authors: Trine Bøegh
authors: TB
authors: Levring
authors: Ann Kathrine
authors: AK
authors: Hansen
authors: Lasse
authors: L
authors: Boding
authors: Jens Peter Holst
authors: JP
authors: Lauritsen
authors: Anders
authors: A
authors: Woetmann
authors: Gottfried
authors: G
authors: Baier
authors: Niels
authors: N
authors: Ødum
authors: Charlotte Menné
authors: CM
authors: Bonefeld
authors: Carsten
authors: C
authors: Geisler
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D021381:Protein Transport; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007527:Isoenzymes; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D005978:Glutathione