The atypical PKCs in inflammation: NF-κB and beyond

Immunol Rev. 2012 Mar;246(1):154-67. doi: 10.1111/j.1600-065X.2012.01093.x.


From the very early days of nuclear factor-κB (NF-κB) research, it was recognized that different protein kinase C (PKC) isoforms might be involved in the activation of NF-κB. Pharmacological tools and pseudosubstrate inhibitors suggested that these kinases play a role in this important inflammatory and survival pathway; however, it was the analysis of several genetic mouse knockout models that revealed the complexity and interrelations between the different components of the PB1 network in several cellular functions, including T-cell biology, bone homeostasis, inflammation associated with the metabolic syndrome, and cancer. These studies unveiled, for example, the critical role of PKCζ as a positive regulator of NF-κB through the regulation of RelA but also its inflammatory suppressor activities through the regulation of the interleukin-4 signaling cascade. This observation is of relevance in T cells, where p62, PKCζ, PKCλ/ι, and NBR1 establish a mesh of interactions that culminate in the regulation of T-cell effector responses through the modulation of T-cell polarity. Many questions remain to be answered, not just from the point of view of the implication for NF-κB activation but also with regard to the in vivo interplay between these pathways in pathophysiological processes like obesity and cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Humans
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Isoenzymes / metabolism*
  • Lymphocyte Activation
  • NF-kappa B / metabolism*
  • Protein Kinase C / metabolism*
  • Receptors, Proteinase-Activated / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Isoenzymes
  • NF-kappa B
  • Receptors, Proteinase-Activated
  • Protein Kinase C
  • protein kinase C lambda