A5063674894- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Erythrocyte Function and Pathophysiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sphingolipid Metabolism and Signaling
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Immune Response and Inflammation
- Blood disorders and treatments
- Adenosine and Purinergic Signaling
- Calcium signaling and nucleotide metabolism
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Inflammasome and immune disorders
- Asthma and respiratory diseases
- Biomedical Research and Pathophysiology
- Nitric Oxide and Endothelin Effects
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- Ion channel regulation and function
- PI3K/AKT/mTOR signaling in cancer
- Inflammatory mediators and NSAID effects
- Systemic Lupus Erythematosus Research
- Phagocytosis and Immune Regulation
- S100 Proteins and Annexins
Université Laval
2011-2024
Centre hospitalier universitaire de Québec
2000-2021
Centre hospitalier de l'Université Laval
1997-2019
Wilfrid Laurier University
1991-2015
Institute for Research in Immunology and Cancer
2005
University of Iowa
2004
Canadian Institutes of Health Research
2003
National Institutes of Health
2002
National Heart Lung and Blood Institute
2002
University of Alberta
2001
The role of GTPase-activating protein (GAP) that deactivates ADP-ribosylation factor 1 (ARF1) during the formation coat I (COPI) vesicles has been unclear. GAP is originally thought to antagonize vesicle by triggering uncoating, but later studies suggest promotes cargo sorting, a process occurs formation. Recent models have attempted reconcile these seemingly contradictory roles suggesting proteins suppress activity formation, whether truly antagonizes recruitment in this not assessed...
Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic acid. In mammalian cells this reaction has been implicated in the recruitment of coatomer Golgi membranes and release nascent secretory vesicles from trans-Golgi network. These observations suggest that PLD is associated with complex; however, date, because its low abundance, intracellular localization characterized only indirectly through overexpression chimeric proteins. We have used highly sensitive antibodies...
Kidney proximal tubule epithelial cells have an extensive apical endocytotic apparatus that is critical for the reabsorption and degradation of proteins traverse glomerular filtration barrier also involved in recycling functionally important plasma membrane transporters. We show here Arf-nucleotide exchange factor, ARNO (ADP-ribosylation factor nucleotide site opener) as well Arf6 Arf1 small GTPases are located kidney receptor-mediated endocytosis pathway, recruitment from cytosol to...
To determine the role of protein tyrosine phosphorylation in activation phospholipase D (PLD), electropermeabilized HL-60 cells labeled [3H]alkyl-phosphatidylcholine were treated with vanadate derivatives. Micromolar concentrations vanadyl hydroperoxide (V(4+)-OOH) induced accumulation tyrosine-phosphorylated proteins. Concomitantly, V(4+)-OOH or a combination and NADPH elicited concentration- time-dependent phosphatidic acid (PtdOH). In presence ethanol sustained formation...
5-Lipoxygenase (5-LO) catalyzes the transformation of arachidonic acid to leukotrienes (LT). In stimulated human PMN, activation 5-LO involves calcium, p38 MAP kinase (p38) phosphorylation, and translocation from cytosol nuclear membranes containing activating protein (FLAP). this study, cAMP-elevating agents such as isoproterenol, prostaglandin E<sub>2</sub>, CGS-21680 (an adenosine A<sub>2a</sub> receptor agonist), type IV phosphodiesterase inhibitor RO 20-1724, adenylate cyclase activator...
Proinflammatory agents were assessed for their capacity to stimulate the expression of inducible cyclooxygenase isoform (COX-2) in human neutrophils. A number agents, including PMA, opsonized bacteria and zymosan, LPS, GM-CSF, TNF-α, fMLP, induced COX-2 protein through signaling pathways involving transcription synthesis events. Northern blots showed that freshly isolated neutrophils expressed low levels mRNA, which rapidly increased after incubation with inflammatory agents....
The inflammatory reaction associated with the deposition of monosodium urate (MSU) crystals in synovial spaces is known to be due interactions polymorphonuclear neutrophils mediated by presently unidentified surface structures. In this study, we have observed that antibodies directed against CD16 (VIFcRIII) and CD11b (VIM12) selectively potently inhibit activation MSU crystals. responses affected include stimulation tyrosine phosphorylation, kinase syk, phosphorylation proto-oncogene Cbl,...
Abstract Phagocytosis is a fundamental feature of the innate immune system, required for antimicrobial defense, resolution inflammation, and tissue remodeling. Furthermore, phagocytosis coupled to diverse range cytotoxic effector mechanisms, including respiratory burst, secretion inflammatory mediators Ag presentation. Phospholipase D (PLD) has been linked regulation subsequent responses, but identity PLD isoform(s) involved molecular mechanisms activation are unknown. We used primary human...
Abstract The glycosylphosphatidyl anchored molecule CD14 to the monocyte membrane plays a prominent role in innate immunity, and paradigms for selective signaling are beginning be elucidated. In this study, transfected human monocytic cell line THP-1 Chinese hamster ovary (CHO) fibroblastic cells were used examine phagocytosis of Mycobacterium bovis bacillus Calmette-Guérin (BCG). Flow cytometry was combined with molecular biochemical approaches demonstrate dual mechanism BCG...
Lysophosphatidic acid (LPA), via interaction with its G-protein coupled receptors, is involved in various pathological conditions. Extracellular LPA mainly produced by the enzyme autotaxin (ATX). Using fibroblast-like synoviocytes (FLS) isolated from synovial tissues of patients rheumatoid arthritis (RA), we studied expression profile LPA-induced cell migration, and interleukin (IL)-8 IL-6 production. We report that FLS express receptors LPA<sub>1-3</sub>. Moreover, exogenously applied...
Phospholipase D (PLD) activation by guanine nucleotides requires protein cofactors from both the membrane and cytosol. The small GTP-binding ADP-ribosylation factor (ARF) has been established as one important component of PLD activation. By stimulating HL-60 cells with various agonists then isolating fraction assaying activity in presence absence GTPγS, we observed that fMet-Leu-Phe (fMLP) phorbol esters induced a potentiation GTPγS-stimulated fractions these cells. Inactive no such...
Docosahexaenoic acid (DHA), ann-3 polyunsaturated fatty that inhibits T lymphocyte activation, has been shown to stimulate phospholipase D (PLD) activity in stimulated human peripheral blood mononuclear cells (PBMC). To elucidate the mechanisms underlying DHA-induced PLD we first characterized expression pattern of PBMC. We show these express PLD1 and PLD2 at protein mRNA level are devoid oleate-dependent activity. DHA enrichment PBMC increased content cell phospholipids, which was directly...
The human phospholipase D1 (hPLD1) has recently been cloned. Although recent data have implicated PLD in receptor-stimulated secretion, the regulation of activity enzymes remains to be clarified. Purified hPLD1 is activated by several cytosolic cofactors among which are protein kinase Cα, ARF, and RhoA. In granulocytes, a strong correlation between tyrosine phosphorylation proteins established. this study, presence HL-60 granulocytes its on residues studied. We generated antipeptide...
Abstract Tyrosine phosphorylation events play major roles in the initiation and regulation of several functional responses human neutrophils stimulated by chemotactic factors such as bacterially derived tripeptide formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). However, links between G protein-coupled receptors, activation tyrosine kinases, neutrophil remain unclear. In present study we assessed effects a Btk inhibitor, leflunomide metabolite analog (LFM-A13), on neutrophils. LFM-A13...
Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic acid, a molecule known have multiple physiological roles, including release of nascent secretory vesicles from the trans-Golgi network. In mammalian cells two forms enzyme, PLD1 and PLD2, been described. We recently demonstrated that is localized Golgi apparatus, nuclei, lesser extent, plasma membrane. Due its low abundance, intracellular localization PLD2 has characterized only indirectly through overexpression...
The generation of diradylglycerol (DRG) and phosphatidic acid (PdtOH) was investigated in neutrophils primed with granulocyte-macrophage colony-stimulating factor (GM-CSF). Mass accumulation DRG PdtOH measured using reversed-phase high performance liquid chromatography thin layer chromatography, respectively. GM-CSF had no direct effect on the levels DRG, but it increased late phase human stimulated FMLP. elevation mass peaked approximately 100 s clearly preceded that which at 150 s....