Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death.

The novel protein kinase C (PKC) isoform, PKC theta, is expressed in a relatively selective manner in T lymphocytes (and muscle). Recent analysis of this PKC isotype in T cells and the characterization of PKC theta-deficient mice revealed important clues about its function and regulation. PKC theta does not have an obvious role in T cell development, but it is essential for the activation of mature T cells. The requirement of PKC theta for T cell activation, proliferation and cytokine production reflects the essential role of this isotype in inducing signaling pathways leading to the activation of the transcription factors AP-1 and NF-kappa B in a T cell-specific manner. A unique feature of PKC theta is its highly selective translocation to the central region of the immunological synapse (IS) in antigen-stimulated T cells, a property apparently important for its proper signaling functions. This localization implies unique pathway(s) that regulate the translocation and/or activation of this enzyme. Our work suggests that sustained PKC theta membrane translocation and phosphorylation are relatively independent of phospholipase C (PLC) activation and diacylglycerol (DAG) production. Instead, a pathway that requires Vav, phosphatidylinositol 3-kinase (PI3-K), Rac1 and actin cytoskeleton reorganization mediates these events. Additionally, PKC theta provides an important survival signal to T cells. Nevertheless, several questions regarding the function and regulation of PKC theta and the identity of its immediate targets/substrates remain open. Resolution of these questions could open the way to the development of selective PKC theta inhibitors, which may have therapeutic potential in immunological diseases and in cancer.