Protein kinase C: a regulator of cytoskeleton remodelling and T-cell migration

Abstract

Protein kinase C (PKC) is a family of ten serine/threonine kinases that have diverse roles in the signalling pathways regulating cellular proliferation, differentiation, apoptosis and immune responses. Elucidating roles for individual PKC isoforms in the immune responses of T-cells have long been a challenging prospect, because these cells are known to express nine of these isoforms. A variety of approaches including the use of knockout mice, overexpression of kinase-inactive mutants, cell-permeable peptides, pharmacological inhibitors and siRNAs have shown that PKCs regulate the production of inflammatory cytokines and the cytotoxic responses of various T-cell subsets. Central to the T-cell immune response is a requirement to migrate to various organs and tissues in search of pathogens and micro-organisms. T-cell migration is guided by specific sets of chemokines and integrin ligands that activate their cognate chemokine receptors and integrins on T-cells, resulting in remodelling of the cytoskeleton and the dynamic protrusive/contractile forces necessary for cell adhesion and motility. In the present article, we review the role of PKC in T-cell migration, with an emphasis on studies that have defined their roles in cytoskeletal remodelling, cell polarity and intracellular trafficking downstream of chemokine receptors and integrins.