ArticleThe Biochemical journal2003
Site-directed mutagenesis of the active site of diacylglycerol kinase alpha: calcium and phosphatidylserine stimulate enzyme activity via distinct mechanisms.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- Review
- The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2022Review
- Elusive structure of mammalian DGKs.Advances in biological regulation · 2022Review
- Review
- Review
- Crystal structure and calcium-induced conformational changes of diacylglycerol kinase α EF-hand domains.Protein science : a publication of the Protein Society · 2019Article
- The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila.Scientific reports · 2018Article
- Exosomes Associated with Human Ovarian Tumors Harbor a Reversible Checkpoint of T-cell Responses.Cancer immunology research · 2018Article
- Article
- The Ligand Binding Landscape of Diacylglycerol Kinases.Cell chemical biology · 2017Article
- Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists.Biochemical pharmacology · 2017Article
- Diacylglycerol Kinase-ε: Properties and Biological Roles.Frontiers in cell and developmental biology · 2016Review
- Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade.Cancer immunology research · 2015Article
- N-Myc and SP regulate phosphatidylserine synthase-1 expression in brain and glial cells.The Journal of biological chemistry · 2011Article
- Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms.Biochimica et biophysica acta · 2009Review
- Molecular determinants for interfacial binding and conformational change in a soluble diacylglycerol kinase.The Journal of biological chemistry · 2009Article
- Dramatic differences in the roles in lipid metabolism of two isoforms of diacylglycerol kinase.Biochemistry · 2008Article
- Analysis of the Staphylococcus aureus DgkB structure reveals a common catalytic mechanism for the soluble diacylglycerol kinases.Structure (London, England : 1993) · 2008Article
- Expression, purification, crystallization and preliminary diffraction studies of the mammalian DAG kinase homologue YegS from Escherichia coli.Acta crystallographica. Section F, Structural biology and crystallization communications · 2006Article
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8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol kinases (DAGKs) catalyse ATP-dependent phosphorylation of sn-1,2-diacylglycerol that arises during stimulated phosphatidylinositol turnover. DAGKa is activated in vitro by Ca2+ and by acidic phospholipids. The regulatory region of DAGKa includes an N-terminal RVH motif and EF hands that mediate Ca2+-dependent activation. DAGKa also contains tandem C1 protein kinase C homology domains. We utilized yeast, Saccharomyces cerevisiae, which lacks an endogenous DAGK, to express DAGKa and to determine the enzymic activities of different mutant forms of pig DAGKa in vitro. Six aspartate residues conserved in all DAGKs were individually examined by site-directed mutagenesis. Five of these aspartate residues reside in conserved blocks that correspond to sequences in the catalytic site of phosphofructokinases. Mutation of D434 (Asp434) or D650 abolished all DAGKa activity, whereas substitution of one among D465, D497, D529 and D697 decreased the activity to 6% or less of that for wild-type DAGKa. Roles of homologous residues in phosphofructokinases suggested that the N-terminal half of the DAGK catalytic domain binds Mg-ATP and the C-terminal half binds diacylglycerol. A DAGKa mutant with its entire regulatory region deleted showed a much decreased activity that was not activated by Ca2+, but still exhibited PS (phosphatidylserine)-dependent activation. Moreover, mutations of aspartate residues at the catalytic domain had differential effects on activation by Ca2+ and PS. These results indicate that Ca2+ and PS stimulate DAGKa via distinct mechanisms.
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