Protein kinase C theta (PKCtheta): a key player in T cell life and death

Abstract

Protein kinase C theta (PKCtheta) is a member of the novel, Ca(2+)-independent PKC subfamily, which plays an important and non-redundant role in several aspects of T cell biology. Much progress has been accomplished in understanding the function of PKCtheta in the immune system and its unique translocation to the immunological synapse in Ag-stimulated T lymphocytes. Biochemical and genetic approaches revealed that PKCtheta is required for the activation of mature T cells as well as for their survival. Mutation of the PKCtheta gene leads to impaired receptor-induced stimulation of the transcription factors AP-1, NF-kappaB and NFAT, which results in defective T cell activation, and to aberrant expression of apoptosis-related proteins, resulting in poor T cell survival. Furthermore, PKCtheta-deficient mice display defects in the differentiation of T helper subsets, particularly in Th2- and Th17-mediated inflammatory responses. Therefore, PKCtheta is a critical enzyme that regulates T cell function at multiple stages, and it represents an attractive drug target for allergic and autoimmune diseases.