title: Diacylglycerol kinases: why so many of them?
abstract: Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating DAG to yield PA. To date, ten mammalian DGK isozymes have been identified. In addition to the C1 domains (protein kinase C-like zinc finger structures) conserved commonly in all DGKs, these isoforms possess a variety of regulatory domains of known and/or predicted functions, such as a pair of EF-hand motifs, a pleckstrin homology domain, a sterile alpha motif domain and ankyrin repeats. Beyond our expectations, recent studies have revealed that DGK isozymes play pivotal roles in a wide variety of signal transduction pathways conducting development, neural and immune responses, cytoskeleton reorganization and carcinogenesis. Moreover, there has been rapidly growing evidence indicating that individual DGK isoforms exert their specific roles through interactions with unique partner proteins such as protein kinase Cs, Ras guanyl nucleotide-releasing protein, chimaerins and phosphatidylinositol-4-phosphate 5-kinase. Therefore, an emerging paradigm for DGK is that the individual DGK isoforms assembled in their own signaling complexes should carry out spatio-temporally segregated tasks for a wide range of biological processes via regulating local, but not global, concentrations of DAG and/or PA.
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan. sakane@sapmed.ac.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakane
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Imai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Kanoh
mesh_terms: D000818:Animals; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D019852:Diacylglycerol Kinase