Diacylglycerol kinases in signal transduction

Abstract

Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol (DAG) to phosphatidic acid. A family of nine mammalian isotypes have been identified. Their primary structure shows a diverse array of conserved domains, such as a catalytic domain, zinc fingers, pleckstrin homology domains and EF-hand structures, known to interact with other proteins, lipids or Ca2+, in signal transduction processes. DGK is believed to act in the phosphoinositide cycle in which DAG is enriched with arachidonoyl moieties, but the majority of DGK isotypes do not show specificity for this DAG species in vitro. This could imply that DGKs may also have other functions in the cell. DGK activity is not only found in membranes, but also in the nucleus and at the cytoskeleton. Agonist-induced translocations of DGK to or from these subcellular sites are known to occur. Some isotypes are contained in signaling complexes in specific association with members of the Rho family of small GTP binding proteins, suggesting that they are involved in Rho-mediated processes such as cytoskeletal reorganization.