The Novel PKCθ from Benchtop to Clinic

J Immunol Res. 2015;2015:348798. doi: 10.1155/2015/348798. Epub 2015 May 19.

Abstract

The protein kinases C (PKCs) are a family of serine/threonine kinases involved in regulating multiple essential cellular processes such as survival, proliferation, and differentiation. Of particular interest is the novel, calcium-independent PKCθ which plays a central role in immune responses. PKCθ shares structural similarities with other PKC family members, mainly consisting of an N-terminal regulatory domain and a C-terminal catalytic domain tethered by a hinge region. This isozyme, however, is unique in that it translocates to the immunological synapse between a T cell and an antigen-presenting cell (APC) upon T cell receptor-peptide MHC recognition. Thereafter, PKCθ interacts physically and functionally with downstream effectors to mediate T cell activation and differentiation, subsequently leading to inflammation. PKCθ-specific perturbations have been identified in several diseases, most notably autoimmune disorders, and hence the modulation of its activity presents an attractive therapeutic intervention. To that end, many inhibitors of PKCs and PKCθ have been developed and tested in preclinical and clinical studies. And although selectivity remains a challenge, results are promising for the future development of effective PKCθ inhibitors that would greatly advance the treatment of several T-cell mediated diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Isoenzymes / immunology
  • Isoenzymes / metabolism
  • Protein Kinase C / immunology*
  • Protein Kinase C / metabolism*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

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