Recent progress on type II diacylglycerol kinases: the physiological functions of diacylglycerol kinase δ, η and κ and their involvement in disease

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DAG) to produce phosphatidic acid (PA) and plays an important role in signal transduction by modulating the balance between these signalling lipids. To date, 10 mammalian DGK isozymes have been identified, and these isozymes are subdivided into five groups according to their structural features. The type II DGKs, consisting of delta 1, delta 2, eta 1, eta 2 and kappa isoforms, possess a pleckstrin homology (PH) domain at their N-termini in addition to the separate catalytic region. Moreover, DGKs delta 1, delta 2 and eta 2 have a sterile alpha motif domain at their C-termini. Recent studies have revealed that type II DGKs play pivotal roles in a wide variety of mammalian signal transduction pathways for cell proliferation and differentiation and glucose metabolism and that the DGKs are involved in cancer, type II diabetes, seizures, hypospadias and bipolar disorder. This review summarizes the current knowledge on the properties and physiological functions of type II DGKs and their involvement in disease.