Phospholipase C Is a Nexus for Rho and Rap-Mediated G Protein
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Population-Specific Associations of Deleterious Rare Variants In
International Journal of Molecular Sciences Article Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients Piotr K. Janicki 1, Ceren Eyileten 2 ID , Victor Ruiz-Velasco 3, Khaled Anwar Sedeek 3, Justyna Pordzik 2, Anna Czlonkowska 2,4, Iwona Kurkowska-Jastrzebska 4 ID , Shigekazu Sugino 1, Yuka Imamura-Kawasawa 5, Dagmara Mirowska-Guzel 2 and Marek Postula 1,2,* ID 1 Perioperative Genomics Laboratory, Penn State College of Medicine, Hershey, PA 17033, USA; [email protected] (P.K.J.); [email protected] (S.S.) 2 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-097 Warsaw, Poland; [email protected] (C.E.); [email protected] (J.P.); [email protected] (A.C.); [email protected] (D.M.-G.) 3 Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA; [email protected] (V.R.-V.); [email protected] (K.A.S.) 4 2nd Department of Neurology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland; [email protected] 5 Genome Sciences Facility, Penn State College of Medicine, Hershey, PA 17033, USA; [email protected] * Correspondence: [email protected]; Tel.: +48-221-166-160 Received: 20 September 2017; Accepted: 7 December 2017; Published: 11 December 2017 Abstract: The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. -
F2RL2 Antibody Cat
F2RL2 Antibody Cat. No.: 56-323 F2RL2 Antibody F2RL2 Antibody immunohistochemistry analysis in formalin fixed and paraffin embedded human heart tissue followed by peroxidase conjugation of the secondary antibody and DAB staining. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This F2RL2 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 21-50 amino acids from the N-terminal region of human F2RL2. TESTED APPLICATIONS: IHC-P, WB For WB starting dilution is: 1:1000 APPLICATIONS: For IHC-P starting dilution is: 1:10~50 PREDICTED MOLECULAR 43 kDa WEIGHT: September 25, 2021 1 https://www.prosci-inc.com/f2rl2-antibody-56-323.html Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: F2RL2 Proteinase-activated receptor 3, PAR-3, Coagulation factor II receptor-like 2, Thrombin ALTERNATE NAMES: receptor-like 2, F2RL2, PAR3 ACCESSION NO.: O00254 GENE ID: 2151 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References Coagulation factor II (thrombin) receptor-like 2 (F2RL2) is a member of the large family of 7-transmembrane-region receptors that couple to guanosine-nucleotide-binding proteins. -
(4,5) Bisphosphate-Phospholipase C Resynthesis Cycle: Pitps Bridge the ER-PM GAP
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Topological organisation of the phosphatidylinositol (4,5) bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER-PM GAP Shamshad Cockcroft and Padinjat Raghu* Dept. of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, UK; *National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore 560065, India Address correspondence to: Shamshad Cockcroft, University College London UK; Phone: 0044-20-7679-6259; Email: [email protected] Abstract Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane– associated diacylglycerol (DG) and the consumption of plasma membrane PI(4,5)P2. Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid. The biochemical intermediates of this cycle and the enzymes that mediate these reactions are topologically distributed across two membrane compartments, the PM and the endoplasmic reticulum (ER). At the plasma membrane, the DG formed during PLC activation is rapidly converted to phosphatidic acid (PA) that needs to be transported to the ER where the machinery for its conversion into PI is localised. Conversely, PI from the ER needs to be rapidly transferred to the plasma membrane where it can be phosphorylated by lipid kinases to regenerate PI(4,5)P2. -
Role of Phospholipases in Adrenal Steroidogenesis
229 1 W B BOLLAG Phospholipases in adrenal 229:1 R29–R41 Review steroidogenesis Role of phospholipases in adrenal steroidogenesis Wendy B Bollag Correspondence should be addressed Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, USA to W B Bollag Department of Physiology, Medical College of Georgia, Augusta University (formerly Georgia Regents Email University), Augusta, GA, USA [email protected] Abstract Phospholipases are lipid-metabolizing enzymes that hydrolyze phospholipids. In some Key Words cases, their activity results in remodeling of lipids and/or allows the synthesis of other f adrenal cortex lipids. In other cases, however, and of interest to the topic of adrenal steroidogenesis, f angiotensin phospholipases produce second messengers that modify the function of a cell. In this f intracellular signaling review, the enzymatic reactions, products, and effectors of three phospholipases, f phospholipids phospholipase C, phospholipase D, and phospholipase A2, are discussed. Although f signal transduction much data have been obtained concerning the role of phospholipases C and D in regulating adrenal steroid hormone production, there are still many gaps in our knowledge. Furthermore, little is known about the involvement of phospholipase A2, Endocrinology perhaps, in part, because this enzyme comprises a large family of related enzymes of that are differentially regulated and with different functions. This review presents the evidence supporting the role of each of these phospholipases in steroidogenesis in the Journal Journal of Endocrinology adrenal cortex. (2016) 229, R1–R13 Introduction associated GTP-binding protein exchanges a bound GDP for a GTP. The G protein with GTP bound can then Phospholipids serve a structural function in the cell in that activate the enzyme, phospholipase C (PLC), that cleaves they form the lipid bilayer that maintains cell integrity. -
Synthesis of Lysophospholipids
Molecules 2010, 15, 1354-1377; doi:10.3390/molecules15031354 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis of Lysophospholipids Paola D’Arrigo 1,2,* and Stefano Servi 1,2 1 Dipartimento di Chimica, Materiali ed Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy 2 Centro Interuniversitario di Ricerca in Biotecnologie Proteiche "The Protein Factory", Politecnico di Milano and Università degli Studi dell'Insubria, Via Mancinelli 7, 20131 Milano, Italy * Author to whom correspondence should be addressed; E-Mail: paola.d’[email protected]. Received: 17 February 2010; in revised form: 4 March 2010 / Accepted: 5 March 2010 / Published: 8 March 2010 Abstract: New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A1 (PLA1), A2 (PLA2) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo- enzymatic procedures leading to 1- and 2-LPLs will be described. -
Antibody Response Cell Antigen Receptor Signaling And
Lysophosphatidic Acid Receptor 5 Inhibits B Cell Antigen Receptor Signaling and Antibody Response This information is current as Jiancheng Hu, Shannon K. Oda, Kristin Shotts, Erin E. of September 24, 2021. Donovan, Pamela Strauch, Lindsey M. Pujanauski, Francisco Victorino, Amin Al-Shami, Yuko Fujiwara, Gabor Tigyi, Tamas Oravecz, Roberta Pelanda and Raul M. Torres J Immunol 2014; 193:85-95; Prepublished online 2 June 2014; Downloaded from doi: 10.4049/jimmunol.1300429 http://www.jimmunol.org/content/193/1/85 Supplementary http://www.jimmunol.org/content/suppl/2014/05/31/jimmunol.130042 http://www.jimmunol.org/ Material 9.DCSupplemental References This article cites 63 articles, 17 of which you can access for free at: http://www.jimmunol.org/content/193/1/85.full#ref-list-1 Why The JI? Submit online. by guest on September 24, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Lysophosphatidic Acid Receptor 5 Inhibits B Cell Antigen Receptor Signaling and Antibody Response Jiancheng Hu,*,1,2 Shannon K. -
P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases
International Journal of Molecular Sciences Review P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases Derek Strassheim 1, Alexander Verin 2, Robert Batori 2 , Hala Nijmeh 3, Nana Burns 1, Anita Kovacs-Kasa 2, Nagavedi S. Umapathy 4, Janavi Kotamarthi 5, Yash S. Gokhale 5, Vijaya Karoor 1, Kurt R. Stenmark 1,3 and Evgenia Gerasimovskaya 1,3,* 1 The Department of Medicine Cardiovascular and Pulmonary Research Laboratory, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] (D.S.); [email protected] (N.B.); [email protected] (V.K.); [email protected] (K.R.S.) 2 Vascular Biology Center, Augusta University, Augusta, GA 30912, USA; [email protected] (A.V.); [email protected] (R.B.); [email protected] (A.K.-K.) 3 The Department of Pediatrics, Division of Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045, USA; [email protected] 4 Center for Blood Disorders, Augusta University, Augusta, GA 30912, USA; [email protected] 5 The Department of BioMedical Engineering, University of Wisconsin, Madison, WI 53706, USA; [email protected] (J.K.); [email protected] (Y.S.G.) * Correspondence: [email protected]; Tel.: +1-303-724-5614 Received: 25 August 2020; Accepted: 15 September 2020; Published: 18 September 2020 Abstract: Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. -
G-Proteins in Growth and Apoptosis: Lessons from the Heart
Oncogene (2001) 20, 1626 ± 1634 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc G-proteins in growth and apoptosis: lessons from the heart John W Adams1,2 and Joan Heller Brown*,1 1University of California, San Diego, Department of Pharmacology, 9500 Gilman Drive, 0636, La Jolla, CA, California 92093- 0636, USA The acute contractile function of the heart is controlled by for proliferation of adult cardiomyocytes. In light of the eects of released nonepinephrine (NE) on cardiac these considerations, it is not immediately obvious that adrenergic receptors. NE can also act in a more chronic cardiomyocyte growth and cardiomyocyte death would fashion to induce cardiomyocyte growth, characterized by be responses critical to the normal function of the heart. cell enlargement (hypertrophy), increased protein synth- In fact, the ability of cardiomyocytes to undergo esis, alterations in gene expression and addition of hypertrophic growth, which includes an increase in cell sarcomeres. These responses enhance cardiomyocyte size, is an important adaptive response to a wide range of contractile function and thus allow the heart to conditions that require the heart to work more compensate for increased stress. The hypertrophic eects eectively. As described below, adaptive or compensa- of NE are mediated through Gq-coupled a1-adrenergic tory cardiomyocyte hypertrophy appears to be regulated receptors and are mimicked by the actions of other in large part through stimulation of G-protein coupled neurohormones (endothelin, prostaglandin F2a angiotensin receptors (GPCRs). Often, the ability of cardiomyocytes II) that also act on Gq-coupled receptors. Activation of to function at high capacity under increased workload phospholipase C by Gq is necessary for these responses, cannot be sustained and the heart transitions into a and protein kinase C and MAP kinases have also been condition in which ventricular failure develops. -
Identification of a Phosphatidic Acid-Preferring Phospholipase Al
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 9574-9578, September 1994 Biochemistry Identification of a phosphatidic acid-preferring phospholipase Al from bovine brain and testis (lysophosphatidic acld/lysophosphoipase/Triton X-100 miceles/phospholpase D/diacylgycerol kinase) HENRY N. HIGGS AND JOHN A. GLOMSET* Departments of Biochemistry and Medicine and Regional Primate Research Center, Howard Hughes Medical Institute, University of Washington, SL-15, Seattle, WA 98195 Contributed by John A. Glomset, May 31, 1994 ABSTRACT Recent experiments in several laboratories drolysis by phospholipase A (PLA) activities, producing have provided evidence that phosphatidic acid functions in cell lysophosphatidic acid (LPA). A PA-specific PLA2 has been signaling. However, the mechaninsm that regulate cellular reported (16), but detailed information about this enzyme is phosphatidic acid levels remain obscure. Here we describe a lacking. Another possibility is that a PLA1 might metabolize soluble phospholipase Al from bovine testis that preferentially PA to sn-2-LPA. Several PLA1 activities have been identified hydrolyzes phosphatidic acid when assayed in Triton X-100 in mammalian tissues, including one found in rat liver plasma micelles. Moreover, the enzyme hydrolyzes phosphatidic acid membrane (17), another found in rat brain cytosol (18, 19), molecular species containing two unsaturated fatty acids in and others found in lysosomes (20, 21). None of these preference to those containing a combination of saturated and enzymes, however, displays a preference for PA as a sub- unsaturated fatty acyl groups. Under certain conditions, the strate. enzyme also displays lysophospholipase activity toward In the present study, we identify and characterize a cyto- lysophosphatidic acid. The phospholipase Al is not likely to be solic PLA1 with a strong preference for PA. -
International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature
0031-6997/02/5402-265–269$7.00 PHARMACOLOGICAL REVIEWS Vol. 54, No. 2 Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics 20204/989285 Pharmacol Rev 54:265–269, 2002 Printed in U.S.A International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature JEROLD CHUN, EDWARD J. GOETZL, TIMOTHY HLA, YASUYUKI IGARASHI, KEVIN R. LYNCH, WOUTER MOOLENAAR, SUSAN PYNE, AND GABOR TIGYI Merck Research Laboratories, La Jolla, California (J.C.); Department of Medicine, University of California, San Francisco, California (E.J.G.); Department of Physiology, University of Connecticut, Farmington, Connecticut (T.L.H.); Department of Biomembrane and Biofunctional Chemisty, Hokkaido University, Sapporo, Japan (Y.I.); Department of Pharmacology, University of Virginia, Charlottesville, Virginia (K.R.L.); Division of Cellular Biochemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands (W.M.); Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland (S.P.); and Department of Physiology, University of Tennessee, Memphis, Tennessee (G.T.) This paper is available online at http://pharmrev.aspetjournals.org Abstract ............................................................................... 265 I. Introduction............................................................................ 265 II. Discovery of lysophospholipid receptors ................................................... 266 III. Receptor nomenclature ................................................................. -
The Role of Platelet Thrombin Receptors PAR1 and PAR4 in Health and Disease
Linköping University Medical Dissertations No 1261 The role of platelet thrombin receptors PAR1 and PAR4 in health and disease Martina Nylander Division of Clinical Chemistry Department of Clinical and Experimental Medicine Linköping University, Sweden Linköping 2011 © Martina Nylander, 2011 Published papers are reprinted with the permission from the copyright holder. The role of platelet thrombin receptors PAR1 and PAR4 in health and disease Cover: A drawing made by the author, illustrating PAR1 & PAR4 cell signaling. Printed in Sweden by LiU-tryck, Linköping, Sweden, 2011 ISBN: 978-91-7393-067-3 ISSN: 0345-0082 ”Life is a mystery” -Julien Offray de La Mettrie To all my dear friends standing steady on earth or flying in the sky ABSTRACT Blood cells are continuously flowing in our systems maintaining haemostasis in the arteries and veins. If a vessel is damaged, the smallest cell fragments in the blood (platelets) are directed to cover the wound and plug the leakage to prevent blood loss. Most of the time platelets stop the blood leak without any difficulties. During other, pathological, circumstances, platelets continue to form a thrombus, preventing the blood flow and may cause myocardial infarction or stroke. Thrombin is the most potent platelet agonist and is a product created in the coagulation cascade. This thesis is focused on the interactions between the two platelet thrombin receptors; protease activated receptors 1 (PAR1) and PAR4 in vitro. We have investigated potential differences between these receptors in several situations associated with cardiovascular disease. First we studied interactions between PAR1 and PAR4 and the oral pathogen Porphyromonas gingivalis (which secretes enzymes, gingipains, with properties similar to thrombin). -
Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats
International Journal of Neuropsychopharmacology Advance Access published March 3, 2015 International Journal of Neuropsychopharmacology, 2015, 1–14 doi:10.1093/ijnp/pyu111 Research Article research article Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats Aline Sayd, MSc; María Antón, MSc; Francisco Alén, PhD; Javier Rubén Caso, Downloaded from PhD; Javier Pavón, PhD; Juan Carlos Leza, MD, PhD; Fernando Rodríguez de Fonseca, MD, PhD; Borja García-Bueno, PhD; Laura Orio PhD Department of Psychobiology, Faculty of Psychology, Complutense University, Complutense University of Madrid http://ijnp.oxfordjournals.org/ (UCM), Madrid, Spain (Ms Antón, and Drs Alén, Rodríguez de Fonseca and Orio); Department of Pharmacology, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)), Madrid, Spain (Ms Sayd, and Drs Leza and García-Bueno); Department of Psychiatry, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain (Dr Caso); UGC Salud Mental, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga-Universidad de Málaga, and Red de Trastornos Adictivos, Málaga, Spain (Drs Pavón and Rodríguez de Fonseca). A.S., M.A., B.G.-B., and L.O. contributed equally to this work. by guest on April 29, 2016 Correspondence: Laura Orio, PhD, Department of Psychobiology, Faculty of Psychology, Complutense University of Madrid, Campus de Somosaguas s/n, 28223 Pozuelo de Alarcón, Madrid (email: [email protected].); and Borja García-Bueno, PhD, Department of Pharmacology, Faculty of Medicine, Complutense University of Madrid, Ciudad Universitaria, 28480 Madrid, Spain ([email protected]). Abstract Background: The acylethanolamides oleoylethanolamide and palmitoylethanolamide are endogenous lipid mediators with proposed neuroprotectant properties in central nervous system (CNS) pathologies.