Heterogeneity of diacylglycerol kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain.

Three different cDNA clones for diacylglycerol (DG) kinase were isolated from a rat brain cDNA library and designated DGK-I, DGK-II and DGK-III. These three encode distinct polypeptides with 58% identity to each other and contain EF-hand motifs, cysteine-rich zinc finger-like sequences and putative ATP-binding sites. A high kinase activity is shown in COS cells transfected with either one of the three cDNAs without substrate specificity among DG species, and the kinase activity is Ca-dependent. The activity for DGK-I is recovered dominantly in the soluble fraction of the cell, that for DGK-II in the particulate fraction; and that for DGK-III equally in both of the fractions. The difference in their expression localization is most noticeable: DGK-I is expressed in oligodendrocytes of the brain as well as T-lymphocytes in the thymus and spleen; DGK-II is expressed in neurons of the caudate-putamen, accumbens nucleus and olfactory tubercle; and DGK-III in the cerebellar Purkinje cells and granule cells. The functional significance of the discovery of three DG kinase isozymes is briefly discussed.