Selective modulation of protein kinase C-theta during T-cell activation

Nature. 1997 Jan 2;385(6611):83-6. doi: 10.1038/385083a0.


Every cell contains many families of protein kinases, and may express several structurally related yet genetically distinct kinases of each family. The activity of the serine/threonine protein kinase C (PKC) enzymes has long been implicated in T-cell activation, but it is not known which members of the PKC family regulate the T-cell response to foreign antigens. The activation of T cells by antigen-presenting cells (APCs) is spatially restricted to their site of contact, where receptors on the T cells engage their counter-receptors on the APCs. We used this localized engagement to identify, at the single-cell level, intracellular proteins involved in the activation process. By digital immunofluorescence microscopy, we localized six isoforms of PKC in antigen-specific T-cell clones activated by APCs. Surprisingly, only PKC-theta translocated to the site of cell contact. Accordingly, in vitro kinase activity assays of PKC immunoprecipitates from the conjugates of T cells and APCs showed a selective increase in the activity of PKC-theta, indicating that the translocated enzyme is active. Several modes of partial T-cell activation that failed to cause PKC-theta translocation also failed to cause T-cell proliferation, further suggesting the involvement of PKC-theta in T-cell activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Biological Transport
  • Cell Line
  • Enzyme Activation
  • Isoenzymes / metabolism*
  • Lymphocyte Activation*
  • Microscopy, Fluorescence
  • Protein Kinase C / metabolism*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured


  • Isoenzymes
  • Receptors, Antigen, T-Cell
  • Protein Kinase C