Diacylglycerol (DAG) plays a central role in both the synthesis of complex lipids and in
intracellular signaling; diacylglycerol
kinase (DGK) catalyzes the
phosphorylation of DAG, which yields
phosphatidic acid. A family of DGKs 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 cause
retinal degeneration. The present invention relates to a novel DGK, designated DGKι, which was isolated from human
retina and brain libraries. DGKι contains two
cysteine-rich repeats, a region similar to the
phosphorylation site domain of MARCKS, a conserved catalytic domain, and four
ankyrin repeats at its C-terminus. By primary structure, DGKι is most similar to human DGKζ and Drosophila rdgA. A>12 kb mRNA for DGKι was detected only in brain and
retina among the tissues examined. In cells transfected with the DGKι cDNA, an approximately 130 kDa
protein was detected by
immunoassay, and activity assays demonstrated that it encodes a functional DAG
kinase. The
protein was found to be in both the
cytoplasm and
nucleus, with this localization controlled by PKC isoforms alpha and gamma. The
gene encoding DGKι was localized to human
chromosome 7q32.3-33, which 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 important
cellular functions in the
retina and brain.