PKCα and PKCβ cooperate functionally in CD3-induced de novo IL-2 mRNA transcription

Immunol Lett. 2013 Mar;151(1-2):31-8. doi: 10.1016/j.imlet.2013.02.002. Epub 2013 Feb 21.

Abstract

The physiological functions of PKCα and PKCθ isotypes downstream of the antigen receptor have been defined in CD3(+) T cells. In contrast, no function of the second conventional PKC member, PKCβ, has been described yet in T cell antigen receptor signalling. To investigate the hypothesis that both conventional PKCα and PKCβ isotypes may have overlapping functions in T cell activation signalling, we generated mice that lacked the genes for both isotypes. We found that PKCα(-/-)/β(-/-) animals are viable, live normal life spans and display normal T cell development. However, these animals possess additive defects in T cell responses in comparison to animals that carry single mutations in these genes. Our studies demonstrate that the activities of PKCα and PKCβ converge to regulate IL-2 cytokine responses in anti-CD3 stimulated primary mouse T cells. Here, we present genetic evidence that PKCα and PKCβ cooperate in IL-2 transcriptional transactivation in primary mouse T cells independently of the actions of PKCθ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / immunology*
  • CD3 Complex / metabolism
  • Immunologic Memory
  • Immunophenotyping
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Phenotype
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism*
  • RNA, Messenger / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation

Substances

  • CD3 Complex
  • Interleukin-2
  • NF-kappa B
  • NFATC Transcription Factors
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Transcription Factor AP-1
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha