Membrane translocation of protein kinase Cθ during T lymphocyte activation requires phospholipase C-γ-generated diacylglycerol

Abstract

Protein kinase Cθ (PKCθ) is the only PKC isoform recruited to the immunological synapse after T cell receptor stimulation, suggesting that its activation mechanism differs from that of the other isoforms. Previous studies have suggested that this selective PKCθ recruitment may operate via a Vav-regulated, cytoskeletal-dependent mechanism, independent of the classical phospholipase C/diacylglycerol pathway. Here, we demonstrate that, together with tyrosine phosphorylation of PKCθ in the regulatory domain, binding of phospholipase C-dependent diacylglycerol is required for PKCθ recruitment to the T cell synapse. In addition, we demonstrate that diacylglycerol kinase α-dependent diacylglycerol phosphorylation provides the negative signal required for PKCθ inactivation, ensuring fine control of the T cell activation response.