title: The atypical PKCs in inflammation: NF-κB and beyond.
abstract: 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.
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Diaz-Meco
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000099293:Protein Kinase C-lambda
chemical_list: D007527:Isoenzymes; D016328:NF-kappa B; D011493:Protein Kinase C; D044462:Receptors, Proteinase-Activated; D000099293:Protein Kinase C-lambda