Phospholipase D1 production of phosphatidic acid at the plasma membrane promotes exocytosis of large dense-core granules at a late stage.
AuthorsZeniou-Meyer M, Zabari N, Ashery U, Chasserot-Golaz S, Haeberlé AM, Demais V, Bailly Y, Gottfried I, Nakanishi H, Neiman AM, Du G, Frohman MA, Bader MF, Vitale N
JournalJ Biol Chem
PubMed ID17540765
'Substantial efforts have recently been made to demonstrate the importance of lipids and lipid-modifying enzymes in various membrane trafficking processes, including calcium-regulated exocytosis of hormones and neurotransmitters. Among bioactive lipids, phosphatidic acid (PA) is an attractive candidate to promote membrane fusion through its ability to change membrane topology. To date, ... More
Cholesterol distribution in the Golgi complex of DITNC1 astrocytes is differentially altered by fresh and aged amyloid beta-peptide-(1-42).
AuthorsIgbavboa U, Pidcock JM, Johnson LN, Malo TM, Studniski AE, Yu S, Sun GY, Wood WG
JournalJ Biol Chem
PubMed ID12584199
'The Golgi complex plays an important role in cholesterol trafficking in cells, and amyloid beta-peptides (Abetas) alter cholesterol trafficking. The hypothesis was tested that fresh and aged Abeta-(1-42) would differentially modify Golgi cholesterol content in DINTC1 astrocytes and that the effects of Abeta-(1-42) would be associated with the region of ... More
The antisignaling agent SC-alpha alpha delta 9, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid, is a structurally unique phospholipid analogue with phospholipase C inhibitory activity.
AuthorsVogt A, Pestell KE, Day BW, Lazo JS, Wipf P,
JournalMol Cancer Ther
PubMed ID12481409
'Phospholipids and lipid second messengers mediate mitogenic signal transduction and oncogenesis, but there have been few successful examples of small molecules that affect biologically important phospholipid metabolism. Here we investigated the actions of a previously described antitumor agent, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid (SC-alpha alpha delta 9), which has antisignaling properties, on ... More
Interfacial sensing by alveolar type II cells: a new concept in lung physiology?
AuthorsRavasio A, Hobi N, Bertocchi C, Jesacher A, Dietl P, Haller T,
JournalAm J Physiol Cell Physiol
PubMed ID21270294
'Alveolar type II (AT II) cells are in close contact with an air-liquid interface (I(AL)). This contact may be of considerable physiological relevance; however, no data exist to provide a satisfying description of this specific microenvironment. This is mainly due to the experimental difficulty to manipulate and analyze cell-air contacts ... More
Loss of the ceramide transfer protein augments EGF receptor signaling in breast cancer.
AuthorsHeering J, Weis N, Holeiter M, Neugart F, Staebler A, Fehm TN, Bischoff A, Schiller J, Duss S, Schmid S, Korte T, Herrmann A, Olayioye MA,
JournalCancer Res
PubMed ID22472120
'Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ... More
Identification of a JAK2-independent pathway regulating growth hormone (GH)-stimulated p44/42 mitogen-activated protein kinase activity. GH activation of Ral and phospholipase D is Src-dependent.
AuthorsZhu T, Ling L, Lobie PE
JournalJ Biol Chem
PubMed ID12218045
'We have demonstrated here that growth hormone (GH) stimulates the formation of the active GTP-bound form of both RalA and RalB in NIH-3T3 cells. Full activation of RalA and RalB by GH required the combined activity of c-Src and JAK2, both kinases activated by GH independent of the other. Activation ... More
Phospholipase D2 mediates signaling by ATPase class I type 8B membrane 1.
AuthorsChen F, Ghosh A, Shneider BL,
JournalJ Lipid Res
PubMed ID23213138
'Functional defects in ATPase class I type 8B membrane 1 (ATP8B1 or familial intrahepatic cholestasis 1, FIC1) lead to cholestasis by mechanism(s) that are not fully understood. One proposed pathophysiology involves aberrant signaling to the bile acid sensor, the farnesoid X receptor (FXR), via protein kinase C ? (PKC?). The ... More
Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner.
'Converging evidence from the analysis of human brain tumors and genetically engineered mice has revealed that the mammalian target of rapamycin (mTOR) pathway is a central regulator of glial and glioma cell growth. In this regard, mutational inactivation of neurofibromatosis-1 (NF1), tuberous sclerosis complex (TSC), and PTEN genes is associated ... More
Phosphorylation-dependent phospholipase D activity of matrix vesicles.
AuthorsBalcerzak M, Pikula S, Buchet R
JournalFEBS Lett
PubMed ID16997299
A progressive hydrolysis of phospholipids was observed during the mineralization process mediated by extracellular matrix vesicles. Increasing levels of different hydrolysis products revealed phospholipase A and D activities. The importance of these enzymes for the mineralization process lies in a high rate of hydrolysis of neutral phospholipids and lower rate ... More
Improving thermostability of phosphatidylinositol-synthesizing Streptomyces phospholipase D.
AuthorsDamnjanovic J, Takahashi R, Suzuki A, Nakano H, Iwasaki Y,
JournalProtein Eng Des Sel
PubMed ID22718790
Aimed to produce thermostable phosphatidylinositol (PI)-synthesizing phospholipase D (PLD), we initiated site-directed combinatorial mutagenesis followed by high-throughput screening. Previous site-directed combinatorial mutagenesis of wild-type Streptomyces PLD produced a mutant, DYR (W187D/Y191Y/Y385R) with PI-synthesizing ability. Deriving PI as a product of transphosphatidylation between phosphatidylcholine and myo-inositol, with myo-inositol in excess at ... More
The B subunits of Shiga-like toxins induce regulated VWF secretion in a phospholipase D1-dependent manner.
AuthorsHuang J, Haberichter SL, Sadler JE,
JournalBlood
PubMed ID22718838
Shiga toxin (Stx) causes diarrhea-associated hemolytic uremic syndrome by damaging renal microvascular endothelium. The pentameric B subunits of Stx types 1 and 2 (Stx1B and Stx2B) are sufficient to stimulate acute VWF secretion from endothelial cells, but Stx1B and Stx2B exert distinct effects on Ca(2+) and cAMP pathways. Therefore, we ... More
Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus.
AuthorsLi X, Gao M, Han X, Tao S, Zheng D, Cheng Y, Yu R, Han G, Schmidt M, Han L,
JournalInfect Immun
PubMed ID22083709
Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In ... More
Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver.
AuthorsMukhopadhyay B, Cinar R, Yin S, Liu J, Tam J, Godlewski G, Harvey-White J, Mordi I, Cravatt BF, Lotersztajn S, Gao B, Yuan Q, Schuebel K, Goldman D, Kunos G,
JournalProc Natl Acad Sci U S A
PubMed ID21383171
The mammalian liver regenerates upon tissue loss, which induces quiescent hepatocytes to enter the cell cycle and undergo limited replication under the control of multiple hormones, growth factors, and cytokines. Endocannabinoids acting via cannabinoid type 1 receptors (CB(1)R) promote neural progenitor cell proliferation, and in the liver they promote lipogenesis. ... More
Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization.
AuthorsGiganti A, Rodriguez M, Fould B, Moulharat N, Cogé F, Chomarat P, Galizzi JP, Valet P, Saulnier-Blache JS, Boutin JA, Ferry G,
JournalJ Biol Chem
PubMed ID18175805
Autotaxin is a type II ectonucleotide pyrophosphate phosphodiesterase enzyme. It has been recently discovered that it also has a lysophospholipase D activity. This enzyme probably provides most of the extracellular lysophosphatidic acid from lysophosphatidylcholine. The cloning and tissue distribution of the three isoforms (imaginatively called alpha, beta, and gamma) from ... More
Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes.
AuthorsAndrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli A
JournalProc Natl Acad Sci U S A
PubMed ID15192144
Blocking the activity of IL-1 beta has entered the clinical arena of treating autoimmune diseases. However, a successful outcome of this approach requires a clear definition of the mechanisms controlling IL-1 beta release. These are still unclear as IL-1 beta, lacking a secretory signal peptide, follows a nonclassical pathway of ... More
CD38 signaling regulates B lymphocyte activation via a phospholipase C (PLC)-gamma 2-independent, protein kinase C, phosphatidylcholine-PLC, and phospholipase D-dependent signaling cascade.
AuthorsMoreno-García ME, López-Bojórques LN, Zentella A, Humphries LA, Rawlings DJ, Santos-Argumedo L
JournalJ Immunol
PubMed ID15728476
The CD38 cell surface receptor is a potent activator for splenic, B lymphocytes. The molecular mechanisms regulating this response, however, remain incompletely characterized. Activation of the nonreceptor tyrosine kinase, Btk, is essential for CD38 downstream signaling function. The major Btk-dependent substrate in B cells, phospholipase C-gamma2 (PLC-gamma2), functions to generate ... More
Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling.
AuthorsKato Y, Lambert CA, Colige AC, Mineur P, Noël A, Frankenne F, Foidart JM, Baba M, Hata R, Miyazaki K, Tsukuda M
JournalJ Biol Chem
PubMed ID15657063
The extracellular pH (pHe) of tumor tissues is often acidic, which can induce the expression of several proteins. We previously showed that production of matrix metalloproteinase-9 (MMP-9) was induced by culturing cells at acidic pHe (5.4-6.5). Here we have investigated the signal transduction pathway by which acidic pHe induces MMP-9 ... More