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Special Issue "Diacylglycerol Kinases in Signal Transduction"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 28 February 2021.

Special Issue Editor

Dr. Gianluca Baldanzi
Website
Guest Editor
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Department of Translational Medicine, Center for Translational Research on Autoimmune & Allergic Diseases, Novara, Italy
Interests: diacylglycerol kinase; lipid signaling; receptor signal transduction; apoptosis; T cell receptor

Special Issue Information

Dear Colleagues,

The phosphorylation of diacylglycerol to phosphatidic acid tunes the level and localization of two key signaling lipids. Thus, diacylglycerol kinases constitute a critical node in signal transduction and a fascinating target for novel therapies. In particular, the increasing number of proteins that are known to be regulated either by diacylglycerol or by phosphatidic acid maintain the great interest in those enzymes. Despite its widespread patterns of expression, the biological function of diacylglycerol kinase has mainly only been explored in the immune and nervous system, while translational approaches have focused on cell transformation and cancer.

By including both research articles and reviews, this Special Issue aims to capture the state of art of the research on the role of diacylglycerol kinase in signaling and phospholipid metabolism. The main focus will be on progressive advancements in the understanding of diacylglycerol kinase regulation and the biological role in different cellular contexts as well as contribution to disease development. Of particular interest are the recent efforts aiming to capitalize the available knowledge in terms of therapeutic advancements using pharmacological inhibitors and genetic tools in spite of the incomplete knowledge of diacylglycerol kinase structure.

Dr. Gianluca Baldanzi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lipid metabolism
  • signal transduction
  • inhibitors
  • genetic models
  • immune function
  • cancer

Published Papers (4 papers)

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Research

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Open AccessArticle
Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination
Int. J. Mol. Sci. 2020, 21(21), 7866; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217866 - 23 Oct 2020
Cited by 2
Abstract
Diacylglycerol kinase γ (DGKγ) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C γ (PKCγ) activity. We previously reported that the basal PKCγ upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKγ knockout [...] Read more.
Diacylglycerol kinase γ (DGKγ) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C γ (PKCγ) activity. We previously reported that the basal PKCγ upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKγ knockout (KO) mice. However, the precise mechanism in impaired cerebellar LTD by upregulated PKCγ has not been clearly understood. Therefore, we first produced Purkinje cell-specific DGKγ KO (tm1d) mice to investigate the specific function of DGKγ in Purkinje cells and confirmed that tm1d mice showed cerebellar motor dysfunction in the rotarod and beam tests, and the basal PKCγ upregulation but not PKCα in the cerebellum of tm1d mice. Then, the LTD-induced chemical stimulation, K-glu (50 mM KCl + 100 µM, did not induce phosphorylation of PKCα and dissociation of GluR2 and glutamate receptor interacting protein (GRIP) in the acute cerebellar slices of tm1d mice. Furthermore, treatment with the PKCγ inhibitor, scutellarin, rescued cerebellar LTD, with the phosphorylation of PKCα and the dissociation of GluR2 and GRIP. In addition, nonselective transient receptor potential cation channel type 3 (TRPC3) was negatively regulated by upregulated PKCγ. These results demonstrated that DGKγ contributes to cerebellar LTD by regulation of the basal PKCγ activity. Full article
(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)
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Review

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Open AccessReview
Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling
Int. J. Mol. Sci. 2020, 21(18), 6861; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186861 - 18 Sep 2020
Abstract
The diacylglycerol kinase family, which can attenuate diacylglycerol signaling and activate phosphatidic acid signaling, regulates various signaling transductions in the mammalian cells. Studies on the regulation of diacylglycerol and phosphatidic acid levels by various enzymes, the identification and characterization of various diacylglycerol and [...] Read more.
The diacylglycerol kinase family, which can attenuate diacylglycerol signaling and activate phosphatidic acid signaling, regulates various signaling transductions in the mammalian cells. Studies on the regulation of diacylglycerol and phosphatidic acid levels by various enzymes, the identification and characterization of various diacylglycerol and phosphatidic acid-regulated proteins, and the overlap of different diacylglycerol and phosphatidic acid metabolic and signaling processes have revealed the complex and non-redundant roles of diacylglycerol kinases in regulating multiple biochemical and biological networks. In this review article, we summarized recent progress in the complex and non-redundant roles of diacylglycerol kinases, which is expected to aid in restoring dysregulated biochemical and biological networks in various pathological conditions at the bed side. Full article
(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)
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Open AccessReview
New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein
Int. J. Mol. Sci. 2020, 21(18), 6794; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186794 - 16 Sep 2020
Cited by 3
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)
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Open AccessReview
Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases
Int. J. Mol. Sci. 2020, 21(15), 5297; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155297 - 26 Jul 2020
Cited by 1
Abstract
An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid [...] Read more.
An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA. Full article
(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)
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