| 摘要 |
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 DGK&igr;, which was isolated from human retina and brain libraries. DGK&igr; 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, DGK&igr; is most similar to human DGK&zgr; and Drosophila rdgA. A>12 kb mRNA for DGK&igr; was detected only in brain and retina among the tissues examined. In cells transfected with the DGK&igr; 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 DGK&igr; 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.
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