• Title, Summary, Keyword: PLD

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The Functional Role of Phospholipase D Isozymes in Apoptosis (세포사멸에서 Phospholipase D 동위효소의 기능적 역할)

  • Min, Do Sik
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1378-1382
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    • 2014
  • Phospholipase D (PLD) catalyzes the hydrolysis of phospholipid to phosphatidic acid (PA), a lipid secondary messenger. Two forms of PLD isozymes, phosphatidylcholine-specific PLD1 and PLD2, have been identified. PLD has emerged as a critical regulator of cell proliferation and survival signaling, and dysregulation of PLD occurs in a various illnesses, including cancer. PLD activity is essential for cell survival and protection from apoptosis. Overexpression of PLD isozymes or PLD-generated PA attenuates the expression of apoptotic genes and confers resistance to apoptosis. The apoptosis-related molecular mechanisms of PLD remain largely unknown. Recently, the dynamics of PLD turnover during apoptosis have been reported. The cleavage of PLD isozymes as specific substrates of caspase differentially regulates apoptosis. PLD1 is cleaved at one internal site, and PLD2 is cleaved two sites at the front of the N-terminus. The cleavage of PLD1 reduces its enzymatic activity, probably via the dissociation of two catalytic motifs, whereas the cleavage of PLD2 does not affect the catalytic motifs and its activity. Thus, PLD2 maintains antiapoptotic capacity, despite its cleavage. Therefore, the differential cleavage pattern of PLD isozymes by caspase affects its enzymatic activity and antiapoptotic function. Thus, PLD is considered a potential target for cancer therapy. We summarize recent studies regarding the functional role of PLD in apoptosis.

Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase

  • Kim, Mi Kyoung;Hwang, Won Chan;Min, Do Sik
    • BMB Reports
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    • v.54 no.2
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    • pp.112-117
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    • 2021
  • Phospholipase D2 (PLD2) has been implicated in the tyrosine kinase-mediated signaling pathways, but the regulation events are yet to be identified. Herein, we demonstrate that pleckstrin homology (PH) domain of PLD2 (PLD2-PH) exerts an antitumorigenic effect via the suppression of PLD2 and focal adhesion kinase (FAK). The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. Furthermore, PLD2 increased tyrosine phosphorylation of FAK. However, ectopic expression of the PLD2-PH competes for binding to FAK and reduces the interaction between PLD2 and FAK, thereby suppressing FAK-induced PLD activation and tyrosine phosphorylation of FAK. The PLD2-PH suppressed the migration and invasion of glioblastoma cells, as well as tumor formation in a xenograft mouse model. This study uncovers a novel role of PLD2-PH as a negative regulator of PLD2 and FAK.

Activation of Phospholipase D2 through Phosphorylation of Tyrosine-470 in Antigen-stimulated Mast Cells

  • Kim Young Mi
    • Journal of Life Science
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    • v.15 no.3
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    • pp.492-498
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    • 2005
  • The mechanism of activation of phospholipase D2 (PLD2) remains undefined although mechanisms have been described for the activation of PLDI. By expression of mutated forms of haemaglutinnin-tagged PLD2 in a mast cell (RBL-2H3) line, we show that PLD2 is phosphorylated at tyrosines -11, -14, and -470 and that tyrosine-470 is critical for activation of PLD2 by antigen. Studies were performed with mutated-DNA constructs for haemaglutinnin-tagged PLD2 in which codons for tyrosine -11, -14, -165, and -470 were mutated to phenylalanine either individually or collectively. Transient expression of these constructs showed that mutation of tyrosine -11, -14, -470, or all tyrosines (all-mutated PLD2) suppressed antigen-induced tyrosine phosphorylation of PLD2 but only the tyrosine-470 mutant failed to be activated by antigen as assessed by in vitro assay of immunoprepitated PLD2 or by assay of PLD in intact cells. The critical role of tyrosine-470 was confirmed in studies with add-back mutants (phenylalanine back to tyrosine) of the all-mutated PLD. The findings provide the first description of a mechanism of activation of PLD2 in a physiological setting.

A Study on the Development of a Tool for PLD Design (PLD 설계용 툴 개발에 관한 연구)

  • Kim, Hee-Suk;Won, Chung-Sang
    • The Transactions of the Korea Information Processing Society
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    • v.1 no.3
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    • pp.391-397
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    • 1994
  • In this paper, we have developed a PLD Designer which is a design tool for digital circuits design using PLD device. PLD designer consists of a state graphic editor to extract boolean equations from state table within 20 states of FSM and a pin map editor to assign pin map for PLD device(PAL16R4, PAL22V10, GAL16V8, etc), which is suitable for extracted boolean equations. Also pin map editor generates a necessary JEDEC file to implement PLD device by using fuse map and checksum algorithm. To verify extracted boolean equation, we have developed simulation test vector generation algorithm. The results of JEDEC files generated by PLD designer is same with the results of JEDEC files generated by PALASM.

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Effect of Sperrnine on Phospholipase D Activity in Rat Brain Mitochondrial Preparation (쥐뇌 미토콘드리아 분획에서 포스포리파제 D에 대한 스퍼민의 영향)

  • Koh, Eun Hie
    • Journal of the Korean Chemical Society
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    • v.44 no.5
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    • pp.448-452
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    • 2000
  • Phospholipase D(PLD) is the enzyme catalyzing the hydrolysis of the terminal phosphcester bond of phospholipid head group to produce phosphatidic acid and the corresponding base. The effect of spermine on the PLD activity of rat brain mitochondrial preparation was investigated. Spermine, in the presence of oleic acid, activates the rat brain mitochondrial PLD, whose effect was further enhanced by the presence of divalent cation, $Ca^{2+}$, $Mg^{2+}$, and $Ba^{2+}$. Among the various monoamines tested, only histamine at the high concentration was effective in activation the PLD. Polylysine increased the PLD activity, particularly, the longer chain of the molecule activated the PLD more effectively. There was no significant difference in the substrate specificity for the PLD activity between phosphatidylcholine(PC) and phoshpatidylethanolamine (PE). This substrate specifitiy is different from the PE specificity reported for the intestinal mitochondrial PLD.

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Carbachol-induced Phosphorylation of Phospholipase D1 through Protein Kinase C is required for the Activation in COS-7 cells

  • Lee, Byoung-Dae;Kim, Yong;Han, Jung-Min;Suh, Pann-Ghill;Ryu, Sung-Ho
    • BMB Reports
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    • v.34 no.2
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    • pp.182-187
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    • 2001
  • Phospholiapse D (PLD), and phosphatidic acid generated by it, have been implicated in receptor-mediated intracellular signaling. Carbachol (CCh) is known to activate PLD1, and protein kinase C (PKC) is known to mediate in this signaling pathway In recent reports (Kim et al., 1999b; Kim et al., 2000), we published our observations of the direct phosphorylation of PLD1 by PKC and we described the phosphorylation-dependent regulation of PLD1 activity. In this study, we investigated the phasphorylation and compartmentalization of PLD1 in terms of CCh signaling in M3 muscarinic receptor (M3R)-expressing COS-7 cells. CCh treatment of COS-7 cells transiently coexpressing PLD1 and M3R stimulated PLD1 activity and induced direct phosphorylation of PLD1 by PKC. The CCh-induced activation and phosphorylation of PLD1 was completely blocked upon pretreatment of the cells with PKC-specific inhibitors. We looked at the localization of the PLD1 phosphorylation by PKC and found that PLD1 was mainly located in the caveolin-enriched membrane (CEM) fraction. Based on these results, we conclude that CCh induces the activation and phosphorylation of PLD1 via PKC and that the phosphorylation of PLD1 occurs in caveolae.

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The Development of PLD Design Tool using the EDIF Netlist (EDIF Netlist를 이용한 PLD 설계용 툴 개발)

  • Kim, Hi-Seok;Byun, Sang-Zoon
    • The Transactions of the Korea Information Processing Society
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    • v.5 no.4
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    • pp.1025-1032
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    • 1998
  • In this paper, the PLD design tool which realizes a digital circuit as PLD, by using EDIF netlist of the digital circuit designed at OrCAD have been developed. This paper is proposed the following algorithms: JIE(Joined Information Extractor) which extracts the connecting information between both cells in order to realize the digital circuit as PLD using the EDIF netlist, FND(Feedback Node Detector) which look into whether feedback exists or not, BEG(Boolean Equation Generator) which generates a boolean equation, and so on. Also, this paper is developed auto-select function which selects the PLD element with consideration of number of I/O variables of the minimized boolean equation, and algorithm generation JEDEC file of GAL6001 and GAL6002, having a forms of EPLD which is bigger than PLD.

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Activation of Phospholipase D in Rat Thymocytes by Sphingosine

  • Lee, Young-kyun;Choi, Myung-Un
    • Bulletin of the Korean Chemical Society
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    • v.23 no.10
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    • pp.1451-1489
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    • 2002
  • Sphingosine is known to regulate a wide range of cell physiology including growth, differentiation, and apoptosis. In this study, we examined the effect of sphingosine on the phospholipase D (PLD) activity in rat thymocytes. Sphingosine potently stimulated PLD in the absence of extracellular calcium, while depletion of intracellular calcium by BAPTA/AM treatment completely blocked activation of PLD by sphingosine. Sphingosine-induced increase of the intracellular calcium concentration was confirmed using a fluorescent calcium indicator Fluo-3/AM. A phosphoinositide-specific phospholipase C inhibitor U73122 partially inhibited the stimulation of PLD by sphingosine. When mouse PLD2 gene was transfected into mouse thymoma EL4 cells, which lack intrinsic PLD activity, sphingosine could stimulate PLD2 significantly while overexpression of human PLD1 had no effect. Taken together, the sphingosine-stimulated PLD activity in rat thymocytes is dependent on the mobilization of intracellular calcium and appears to be due to the PLD2 isoform.

Identification and Characterization of Phytochrome-Regulated Phospholipase D in Oat Cells (Avena sativa L.)

  • Park, Cheon;Park, Moon-Hwan;Chae, Quae
    • BMB Reports
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    • v.29 no.6
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    • pp.535-539
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    • 1996
  • The activation of phospholipase D (PLD) catalyzes hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA) and choline in plants as well as animals. To determine the presence of PLD in oat cells, we prepared inside-out plasma membrane and cytosolic fractions from oat tissues. PLD activities in both cytosol and plasma membrane were detected by ion chromatography method. The activity of PLD in plasma membrane was dependent upon $Ca^{2+}$ concentration and was heat stable. To investigate whether G-protein couples to PLD, the effects of $GTP{\gamma}S$ and $GDP{\beta}S$ on the PLD activity were measured. PLD activity was dramatically increased 300~400% in the presence of 50 ${\mu}M$ $GTP{\gamma}S$ but not in the presence of 50 ${\mu}M$ $GDP{\beta}S$. These results indicate that G-protein may be involved in regulation of PLD activity. To identify whether PLD is regulated by red light receptor, phytochrome, we irradiated red, far-red, or red/far-red/red light on oat protoplasts. PLD activity has increased 5-fold and 3-fold by treatment with red light and red/far-red/red light, respectively. In contrast, irradiation with far-red light had little or no effect on PLD activity. These results suggest that phytochrome regulates PLD activity through activation of G-protein in oat cells.

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Over-Expression of Phospholipase D Isozymes Down-Regulates Protein Kinase CKII Activity via Proteasome-Dependent CKIIβ Degradation in NIH3T3 Cells

  • Yoon, Soo-Hyun;Min, Do Sik;Bae, Young-Seuk
    • Molecules and Cells
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    • v.27 no.3
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    • pp.299-305
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    • 2009
  • Over-expression of phospholipase D (PLD) 1 or PLD2 down-regulated CKII activity in NIH3T3 cells. The same results were found with catalytically inactive mutants of PLD isozymes, indicating that the catalytic activity of PLD is not required for PLD-mediated CKII inhibition. Consistent with this, 1-butanol did not alter CKII activity. The reduction in CKII activity in PLD-over-expressing NIH3T3 cells was due to reduced protein level, but not mRNA level, of the $CKII{\beta}$ subunit. This PLD-induced $CKII{\beta}$ degradation was mediated by ubiquitin-proteasome machinery, but MAP kinase and mTOR were not involved in $CKII{\beta}$ degradation. PLD isozymes interacted with the $CKII{\beta}$ subunit. Immunocytochemical staining revealed that PLD and $CKII{\beta}$ colocalize in the cytoplasm of NIH3T3 cells, especially in the perinuclear region. PLD binding to $CKII{\beta}$ inhibited $CKII{\beta}$ autophosphorylation, which is known to be important for $CKII{\beta}$ stability. In summary, the current data indicate that PLD isozymes can down-regulate CKII activity through the acceleration of $CKII{\beta}$ degradation by ubiquitin-proteasome machinery.