Protein kinase C theta affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells

J Exp Med. 2003 Jun 2;197(11):1525-35. doi: 10.1084/jem.20020234.

Abstract

Protein kinase C (PKC)theta is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-kappaB. To study the physiological function of PKCtheta, we used gene targeting to generate a PKCtheta null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCtheta-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCtheta primarily abrogates NFAT transactivation. In contrast, NF-kappaB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCtheta plays a critical and nonredundant role in T cell receptor-induced NFAT activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Calcium Signaling*
  • Cells, Cultured
  • DNA / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Isoenzymes
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Transcription Factors
  • DNA
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta