DGK-θ: Structure, Enzymology, and Physiological Roles

Abstract

Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al., 2011; Tu-Sekine et al., 2013) among others]. We now know there are ten mammalian DGKs that are organized into five classes. DGK-θ is the lone member of the Type V class of DGKs and remains as one of the least studied. This review focuses on our current understanding of the structure, enzymology, regulation, and physiological roles of this DGK and suggests some future areas of research to understand this DGK isoform.

Keywords: diacylglycerol kinase; interfacial enzymology; phosphatidic acid; regulation; synaptic vesicle cycle.

Figure 1

Linear domain structure of DGK-θ.

Figure 2

Proposed model for DGK-θ membrane association and activation. In this model, DGK-θ exists in an auto-inhibited state which can bind to membranes in the presence or absence of a protein activator containing a polybasic region. Following membrane binding, full activation is achieved when a triad complex forms composed of enzyme, polybasic protein, and phospholipid activator.