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

Marina Rode von Essen; Martin Kongsbak; Trine Bøegh Levring; Ann Kathrine Hansen; Lasse Boding; Jens Peter Holst Lauritsen; Anders Woetmann; Gottfried Baier; Niels Odum; Charlotte Menné Bonefeld; Carsten Geisler

doi:10.1002/eji.201243140

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

Marina Rode von Essen, Martin Kongsbak, Trine Bøegh Levring, Ann Kathrine Hansen, Lasse Boding, Jens Peter Holst Lauritsen, Anders Woetmann, Gottfried Baier, Niels Odum, Charlotte Menné Bonefeld, Carsten Geisler

Department of Immunology and Microbiology

11 Citations (Scopus)

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.

Original language	English
Journal	European Journal of Immunology
Volume	43
Issue number	6
Pages (from-to)	1659-66
Number of pages	8
ISSN	0014-2980
DOIs	https://doi.org/10.1002/eji.201243140
Publication status	Published - Jun 2013

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@article{dd0bf22e220141e8933184b785352f28,

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 na{\"i}ve 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 na{\"i}ve 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 na{\"i}ve T cells. Our observations underscore the existence of major differences in TCR signaling in na{\"i}ve versus primed T cells.",

author = "{von Essen}, {Marina Rode} and Martin Kongsbak and Levring, {Trine B{\o}egh} and Hansen, {Ann Kathrine} and Lasse Boding and Lauritsen, {Jens Peter Holst} and Anders Woetmann and Gottfried Baier and Niels Odum and Bonefeld, {Charlotte Menn{\'e}} and Carsten Geisler",

note = "{\textcopyright} 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2013",

month = jun,

doi = "10.1002/eji.201243140",

language = "English",

volume = "43",

pages = "1659--66",

journal = "European Journal of Immunology",

issn = "0014-2980",

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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

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 -

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

Abstract

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