title: Accumulating insights into the role of phospholipase D2 in human diseases.
abstract: Phospholipase D2 (PLD2) is a lipid-signaling enzyme that produces the signaling molecule phosphatidic acid (PA) by catalyzing the hydrolysis of phosphatidylcholine (PC). The molecular characteristics of PLD2, the mechanisms of regulation of its activity, its functions in the signaling pathway involving PA and binding partners, and its role in cellular physiology have been extensively studied over the past decades. Although several potential roles of PLD2 have been proposed based on the results of molecular and cell-based studies, the pathophysiological functions of PLD2 in vivo have not yet been fully investigated at the organismal level. Here, we address accumulated evidences that provide insight into the role of PLD2 in human disease. We summarize recent studies using animal models that provide direct evidence of the function of PLD2 in several pathological conditions such as vascular disease, immunological disease, and neurological disease. In light of the use of recently developed PLD2-specific inhibitors showing potential in alleviating pathological conditions, improving our understanding of the role of PLD2 in human disease would be necessary to target the regulation of PLD2 activity as a therapeutic strategy.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Jaewang
authors.initials: J
authors.lastname: Ghim
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Chaithanya
authors.initials: C
authors.lastname: Chelakkot
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea. Electronic address: sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007155:Immunologic Factors / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009422:Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors / Q000627:therapeutic use*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014652:Vascular Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D007155:Immunologic Factors; D018696:Neuroprotective Agents; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D064801:Phospholipase A2 Inhibitors; C105606:phospholipase D2; D010739:Phospholipase D
keywords: Immunological disease; Neurological disorder; Pathological function; Phospholipase D2; Vascular disease