Last update 01 Nov 2024

PLD2

Last update 01 Nov 2024

Basic Info

Synonyms

Choline phosphatase 2, hPLD2, Phosphatidylcholine-hydrolyzing phospholipase D2

+ [4]

Introduction

Function as phospholipase selective for phosphatidylcholine (PubMed:9582313). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (By similarity).

Drugs associated with PLD2

ML299

Target

PLD1 x PLD2

Mechanism

PLD1 inhibitors [+1]

Active Org.

Vanderbilt University Medical Center

Originator Org.

Vanderbilt University Medical Center

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ML298

Target

PLD2

Mechanism

PLD2 inhibitors

Active Org.

Vanderbilt University Medical Center

Originator Org.

Vanderbilt University Medical Center

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PLD1/PLD2 inhibitor(Vanderbilt University)

Target

PLD1 x PLD2

Mechanism

PLD1 inhibitors [+1]

Active Org.

Vanderbilt University

Originator Org.

Vanderbilt University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PLD2

100 Translational Medicine associated with PLD2

0 Patents (Medical) associated with PLD2

696

Literatures (Medical) associated with PLD2

01 Dec 2024·Life Sciences

Phospholipase D2 drives cellular lipotoxicity and tissue inflammation in alcohol-associated liver disease

Article

Author: Xu, Huihui ; Li, Jichen ; Ge, Hailong ; Wang, Hansong ; Guo, Yan ; Li, Jicen ; Miao, Xiulian ; Wang, Yu ; Wang, Jianguo

AIMSExcessive alcohol consumption leads to alcoholic liver disease (ALD), a major contributing factor to cirrhosis and hepatocellular carcinoma. In the present study we investigated the involvement of phospholipase D2 (PLD2) in the pathogenesis of ALD.METHODS AND MATERIALSALD was induced in mice by chronic and binge ethanol feeding (the NIAAA model). Cellular transcriptome was examined by RNA-seq.KEY FINDINGSAnalysis of RNA-seq datasets indicated that PLD2 expression was up-regulated in liver tissues and in hepatocytes during ALD pathogenesis. Exposure of hepatocytes to ethanol treatment led to an increase in PLD2 expression. Similarly, ethanol feeding in mice stimulated PLD2 expression in the liver. On the contrary, PLD2 knockdown in hepatocytes down-regulated expression of pro-inflammatory and pro-lipogenic genes and dampened lipid accumulation. Consistently, PLD2 knockdown in mice significantly ameliorated ALD pathogenesis as evidenced by reduced steatosis and hepatic inflamamation. RNA-seq identified several metabolic pathways that were influenced by PLD2 deficiency.SIGNIFICANCEOur data demonstrate that PLD2 is a novel regulator of ALD and suggest that small-molecule PLD2 inhibitors can be considered as a reasonable strategy for ALD treatment.

01 Jul 2024·International Journal of Biological Macromolecules

RNA binding protein RALY facilitates colorectal cancer metastasis via enhancing exosome biogenesis in m6A dependent manner

Article

Author: Ji, Qing ; Ge, Guangbo ; Han, Yicun ; Li, Hongshan ; Li, Ling ; Zhou, Jing

Tumor metastasis is the leading cause of cancer-related death in patients with colorectal cancer (CRC). Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins, involved in the tumorigenesis and metastasis of various cancers. However, the molecular mechanisms of hnRNPs in CRC metastasis remain unclear. This study aims to uncover the pivotal roles and molecular mechanisms of hnRNPs in CRC metastasis. Clinical database analysis suggested that the expression of hnRNP-Associated with Lethal Yellow (RALY, an important member of hnRNPs) was strongly correlated with the aggressiveness and survival of CRC patients. Gain- and loss-of-function studies demonstrated that RALY promotes the production of exosomes by increasing the formation of multivesicular bodies (MVBs) and enhancing the fusion of MVBs with the plasma membrane. Notably, RALY directly interacts with phospholipase D2 (PLD2) to enable exosome biogenesis, and cooperates with RBM15b to control PLD2 mRNA stability in an m6A-dependent manner. RALY-mediated exosome secretion activates pro-tumor macrophages and further facilitates CRC metastasis, while rescue experiments in vivo further confirmed that RALY-mediated exosome biogenesis facilitates CRC metastasis. Collectively, our findings demonstrate that RALY promotes exosome biogenesis and facilitates colorectal cancer metastasis by upregulating PLD2 and enhancing exosome production in an m6A-dependent manner, suggesting potential therapeutic strategies for combating CRC metastasis.

01 Jul 2024·Arthritis & Rheumatology

Phosphatidic Acid Promoting the Generation of Interleukin‐17A Producing Double‐Negative T Cells by Enhancing mTORC1 Signaling in Lupus

Article

Author: Xu, Xuefeng ; Tsao, Betty P ; Zheng, Yuanyuan ; Tang, Xiaojun ; Zhao, Nan ; Li, Wenjing ; Sun, Lingyun ; Feng, Xuebing

ObjectiveThe goal was to investigate the role and intracellular regulatory mechanisms of double‐negative T (DNT) cells in the pathogenesis of systemic lupus erythematosus (SLE).MethodsDNT cells were assessed in murine models, patients with SLE, and controls using flow cytometry (FCM). DNT cells from either resiquimod (R848) or vehicle‐treated C57BL/6 (B6) mice were cultured with B cells from R848‐treated mice to explore functions. Differential mechanistic target of rapamycin (mTOR) pathway signaling in DNT cells measured using FCM and quantitative polymerase chain reaction was validated by rapamycin inhibition. Candidate lipid metabolites detected using liquid chromatography with electrospray ionization mass spectrometry/mass spectrometry were functionally assessed in DNT cell cultures.ResultsDNT cells were markedly increased in both spontaneous and induced mouse lupus models and in patients with SLE. Expanded DNT cells from R848‐treated B6 mice produced elevated interleukin (IL)‐17A and IgG with increased germinal center B (GCB) cells. Expansion of DNT cells associated with activation of mTORC1 pathway that both IL‐17A levels and the number of DNT cells exhibited dose‐dependent reduction with rapamycin treatment. Lipidomics studies revealed differential patterns of lipid metabolites in T cells of R848‐treated mice. Among candidate metabolites, elevated phosphatidic acid (PA) that was partially controlled by phospholipase D2 increased the expression of the mTORC1 downstream target p‐S6 and positively expanded IL‐17A–producing DNT cells. Similarly, elevated proportions of circulating DNT cells in patients with SLE correlated with disease activity and proteinuria, and IL‐17A secretion was elevated after in vitro PA stimulation.ConclusionThe accumulation of PA in T cells could activate the mTORC1 pathway, promoting DNT cell expansion and IL‐17A secretion, resulting in GCB cell abnormalities in lupus.

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PLD2

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