Next Article in Journal
Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients
Next Article in Special Issue
Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling
Previous Article in Journal
Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer
Previous Article in Special Issue
Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
Review

New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein

Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6794; https://doi.org/10.3390/ijms21186794
Received: 26 August 2020 / Revised: 11 September 2020 / Accepted: 14 September 2020 / Published: 16 September 2020
(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)
Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Mammalian DGK consists of ten isozymes (α–κ) and governs a wide range of physiological and pathological events, including immune responses, neuronal networking, bipolar disorder, obsessive-compulsive disorder, fragile X syndrome, cancer, and type 2 diabetes. DG and PA comprise diverse molecular species that have different acyl chains at the sn-1 and sn-2 positions. Because the DGK activity is essential for phosphatidylinositol turnover, which exclusively produces 1-stearoyl-2-arachidonoyl-DG, it has been generally thought that all DGK isozymes utilize the DG species derived from the turnover. However, it was recently revealed that DGK isozymes, except for DGKε, phosphorylate diverse DG species, which are not derived from phosphatidylinositol turnover. In addition, various PA-binding proteins (PABPs), which have different selectivities for PA species, were recently found. These results suggest that DGK–PA–PABP axes can potentially construct a large and complex signaling network and play physiologically and pathologically important roles in addition to DGK-dependent attenuation of DG–DG-binding protein axes. For example, 1-stearoyl-2-docosahexaenoyl-PA produced by DGKδ interacts with and activates Praja-1, the E3 ubiquitin ligase acting on the serotonin transporter, which is a target of drugs for obsessive-compulsive and major depressive disorders, in the brain. This article reviews recent research progress on PA species produced by DGK isozymes, the selective binding of PABPs to PA species and a phosphatidylinositol turnover-independent DG supply pathway. View Full-Text
Keywords: diacylglycerol kinase; phosphatidic acid; phosphatidic acid-binding protein; fatty acid; docosahexaenoic acid; phosphatidylinositol turnover; lipid sensor diacylglycerol kinase; phosphatidic acid; phosphatidic acid-binding protein; fatty acid; docosahexaenoic acid; phosphatidylinositol turnover; lipid sensor
Show Figures

Figure 1

MDPI and ACS Style

Sakane, F.; Hoshino, F.; Murakami, C. New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein. Int. J. Mol. Sci. 2020, 21, 6794. https://doi.org/10.3390/ijms21186794

AMA Style

Sakane F, Hoshino F, Murakami C. New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein. International Journal of Molecular Sciences. 2020; 21(18):6794. https://doi.org/10.3390/ijms21186794

Chicago/Turabian Style

Sakane, Fumio, Fumi Hoshino, and Chiaki Murakami. 2020. "New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein" International Journal of Molecular Sciences 21, no. 18: 6794. https://doi.org/10.3390/ijms21186794

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop