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

Eur J Immunol. 2013 Jun;43(6):1659-66. doi: 10.1002/eji.201243140. Epub 2013 Apr 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Glutathione / metabolism
  • Humans
  • Isoenzymes / metabolism*
  • Lymphocyte Activation
  • Oxidation-Reduction
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein Transport
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Isoenzymes
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • Glutathione