The cloning and characterization of a novel human diacylglycerol kinase, DGK iota

Diacylglycerol (DAG) plays a central role in both the synthesis of complex lipids and in intracellular signaling; diacylglycerol kinase (DGR) catalyze s the phosphorylation of DAG, which yields phosphatidic acid. A family of D GKs has been identified in multicellular organisms over the past few years, but the physiological function(s) of this diversity is not clear. One clue has come from the Drosophila DGK2, rdgA, since mutations in this gene caus e retinal degeneration. We isolated a novel DGK, which we designated DGK io ta, from human retina and brain libraries. DGK iota contains two cysteine-r ich repeats, a region similar to the phosphorylation site domain of myristo ylated alanine-rich C kinase substrate, a conserved catalytic domain, and f our ankyrin repeats at its C terminus. By primary structure, it is most sim ilar to human DGK zeta and Drosophila rdgA, An >12-kilobase mRNA for DGK io ta was detected only in brain and retina among the tissues examined. In cel ls transfected with the DGK iota cDNA, we detected an approximately 130-kDa protein by immunoassay, and activity assays demonstrated that it encodes a functional DAG kinase, The protein was found to be in both the cytoplasm a nd nucleus with the localization controlled by PRC isoforms alpha and gamma . The gene encoding DGK iota was localized to human chromosome 7q32.3-33, w hich is known to be a locus for an inherited form of retinitis pigmentosa. These results have defined a novel isoform of DAG kinase, which may have im portant cellular functions in the retina and brain.