Insights Derived from the Structures of the Ser/Thr Phosphatases
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ATP-Induced Focal Adhesion Kinase Activity Is Negatively Modulated by Phospholipase D2 in PC12 Cells
EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 33, No. 3, 150-155, September 2001 ATP-induced focal adhesion kinase activity is negatively modulated by phospholipase D2 in PC12 cells Yoe-Sik Bae1 and Sung Ho Ryu1,2 Introduction 1 Division of Molecular and Life Sciences, Pohang University of Purinergic receptors have been reported to play impor- Science and Technology, Pohang 790-784, Korea tant roles on the regulation of neuronal cell functions 2 Corresponding author: Tel, +82-54-279-2292; (Communi et al., 2000; Di Iorio et al., 1998). ATP, a Fax, +82-54-279-2199; E-mail, [email protected] ligand for the receptors modulate various cellular re- sponses such as mitogenic and morphogenic activity in Accepted 18 September 2001 PC12 rat pheochromocytoma cells (Neary et al., 1996; Soltoff et al., 1998; Schindelholz et al., 2000). Stimu- Abbreviations: Fak, focal adhesion kinase; PLD, phospholipase D; lation of cells with ATP induces tyrosine phosphorylation PA, phosphatidic acid; PC, phosphatidylcholine; DAG, diacylglyc- of several cytoskeletal proteins and focal adhesion erol; PBt, phosphatidylbutanol; PKC, protein kinase C; PAP, phos- molecules such as focal adhesion kinase (Fak), proline- phatidic acid phosphohydrolase rich tyrosine kinase (Pyk2), and paxillin (Soltoff et al., 1998; Schindelholz et al., 2000). Since these cytosk- eleton-associated proteins have been regarded as important factors for the regulation of neuronal cell Abstract functions, the study on the regulatory mechanism for the proteins remains an important issue. Extracellular ATP has been known to modulate vari- Phospholipase D (PLD) catalyzes the hydrolysis of ous cellular responses including mitogenesis, secre- phosphatidylcholine (PC) into phosphatidic acid (PA) tion and morphogenic activity in neuronal cells. -
Datasheet for Protein Phosphatase 1 (PP1) (P0754; Lot 0121306)
Supplied in: 200 mM NaCl, 50 mM HEPES Unit Definition: One unit is defined as Notes On Use: Avoid freeze/thaw cycles. Can be Protein the amount of enzyme that hydrolyzes 1 nmol of stored for 1 week or less at –20°C. (pH 7.0 @ 25°C), 1 mM MnCl2, 0.1 mM EGTA, Phosphatase 1 2.5 mM dithiothreitol, 0.025% Tween-20 and p-Nitrophenyl Phosphate (50 mM) (NEB #P0757) 50% glycerol. Store at –70°C in 1 minute at 30°C in a total reaction volume of The following information can be used as (PP1) 50 µl. suggested initial conditions for dephosphorylation 1-800-632-7799 Applications: PP1 can be used to release of proteins with PP1. [email protected] phosphate groups from phosphorylated serine, Specific Activity: ~ 80,000 units/mg. www.neb.com 0.1 unit of PP1 removes ~100% of phosphates P0754S 012130614061 threonine and tyrosine residues in proteins. Note that different proteins are dephosphorylated at Molecular Weight: 37.5 kDa. (0.5 nmol) from phosphoserine/threonine different rates. residues in phosphorylase a as well as in P0754S r y Purity: PP1 has been purified to > 90% phosphorylated myelin basic protein (phospho- 100 units 2,500 U/ml Lot: 0121306 Reagents Supplied with Enzyme: homogeneity as determined by SDS-PAGE and MyBP, 18.5 kDa) in 30 minutes in a 50 µl reaction. RECOMBINANT Store at –70°C Exp: 6/14 10X NEBuffer for Protein MetalloPhosphatases Coomassie Blue staining. The concentration of phospho-MyBP is 10 µM (PMP) with respect to phosphate. Description: Protein Phosphatase 1 (PP1) is a 10X MnCl2 (10 mM) Quality Assurance: PP1 contains no detectable Mn2+-dependent protein phosphatase with activity protease activity. -
Circulating Supar in Two Cohorts of Primary FSGS
CLINICAL RESEARCH www.jasn.org Circulating suPAR in Two Cohorts of Primary FSGS † ‡ Changli Wei,* Howard Trachtman, Jing Li,* Chuanhui Dong, Aaron L. Friedman,§ | | | Jennifer J. Gassman, June L. McMahan, Milena Radeva, Karsten M. Heil,¶ †† ‡‡ Agnes Trautmann,¶ Ali Anarat,** Sevinc Emre, Gian M. Ghiggeri, Fatih Ozaltin,§§ || ††† Dieter Haffner, Debbie S. Gipson,¶¶ Frederick Kaskel,*** Dagmar-Christiane Fischer, ‡‡‡ Franz Schaefer,¶ and Jochen Reiser, for the PodoNet and FSGS CT Study Consortia Departments of *Medicine and ‡Neurology, University of Miami Miller School of Medicine, Miami, Florida; †Department of Pediatrics, NYU Langone Medical Center, New York, New York; §Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; |Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio; ¶Center for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany; **Department of Pediatric Nephrology, Cukurova University School of Medicine, Adana, Turkey; ††Department of Pediatrics, Istanbul Medical Faculty, University of Istanbul, Istanbul, Turkey; ‡‡Division of Nephrology, Dialysis, and Transplantation, Laboratory on Pathophysiology of Uremia, G. Gaslini Children’s Hospital, Genoa, Italy; §§Pediatric Nephrology Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey; ||Department of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, Hannover, Germany; ¶¶Department of Pediatrics, University of Michigan, Ann Arbor, Michigan; ***Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York; †††Department of Pediatrics, Rostock University Hospital, Rostock, Germany; and ‡‡‡Department of Medicine, Rush University Medical Center, Chicago, Illinois ABSTRACT Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to pri- mary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. -
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. -
Regulation of Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase (PDE1): Review
95-105 5/6/06 13:44 Page 95 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18: 95-105, 2006 95 Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1): Review RAJENDRA K. SHARMA, SHANKAR B. DAS, ASHAKUMARY LAKSHMIKUTTYAMMA, PONNIAH SELVAKUMAR and ANURAAG SHRIVASTAV Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Cancer Research Division, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon SK S7N 4H4, Canada Received January 16, 2006; Accepted March 13, 2006 Abstract. The response of living cells to change in cell 6. Differential inhibition of PDE1 isozymes and its environment depends on the action of second messenger therapeutic applications molecules. The two second messenger molecules cAMP and 7. Role of proteolysis in regulating PDE1A2 Ca2+ regulate a large number of eukaryotic cellular events. 8. Role of PDE1A1 in ischemic-reperfused heart Calmodulin-stimulated cyclic nucleotide phosphodiesterase 9. Conclusion (PDE1) is one of the key enzymes involved in the complex interaction between cAMP and Ca2+ second messenger systems. Some PDE1 isozymes have similar kinetic and 1. Introduction immunological properties but are differentially regulated by Ca2+ and calmodulin. Accumulating evidence suggests that the A variety of cellular activities are regulated through mech- activity of PDE1 is selectively regulated by cross-talk between anisms controlling the level of cyclic nucleotides. These Ca2+ and cAMP signalling pathways. These isozymes are mechanisms include synthesis, degradation, efflux and seque- also further distinguished by various pharmacological agents. stration of cyclic adenosine 3':5'-monophosphate (cAMP) and We have demonstrated a potentially novel regulation of PDE1 cyclic guanosine 3':5'- monophosphate (cGMP) within the by calpain. -
Accession Description Biological Process Cellular Component P-Value SCZ/CTRL Ration A4FU69 EF-Hand Calcium-Binding Domain-Contai
Accession Description Biological Process Cellular component p-Value SCZ/CTRL ration A4FU69 EF-hand calcium-binding domain-containing protein 5 0,001101 2,724427411 A4UGR9 Xin actin-binding repeat-containing protein 2 Cytoskeletal anchoring Cytoplasm 0,006756 1,413953388 A6NCE7 Microtubule-associated proteins 1A/1B light chain 3 beta 2 Cytoplasm 0,001417 1,99612969 B2RPK0 Putative high mobility group protein B1-like 1 0,032314 1,590743352 O00231 26S proteasome non-ATPase regulatory subunit 11 Protein metabolism Cytoplasm; Nucleus 0,000029 1,428664042 O00232 26S proteasome non-ATPase regulatory subunit 12 Protein metabolism Cytoplasm 0,008566 1,544545922 O00264 Membrane-associated progesterone receptor component 1 Cell communication Plasma membrane 0,001459 2,322924147 O00429 Dynamin-1-like protein Mitochondrion organization and biogenesis Cytoplasm 0,006560 0,06391487 O00567 Nucleolar protein 56 Regulation of nucleotide metabolism Nucleus 0,007330 3,842896338 O14737 Programmed cell death protein 5 Apoptosis Cytoplasm; Nucleus 0,006358 3,836727237 O14818 Proteasome subunit alpha type-7 Protein metabolism Cytoplasm 0,030521 1,893928387 O14979 Heterogeneous nuclear ribonucleoprotein D-like Regulation of nucleotide metabolism Nucleus 0,000637 2,150005885 O15078 Centrosomal protein of 290 kDa 0,015359 14,26648619 O15347 High mobility group protein B3 Regulation of nucleotide metabolism Nucleus 0,005500 1,364309014 O15540 Fatty acid-binding protein_ brain Transport Cytoplasm 0,000087 3,125786118 O43237 Cytoplasmic dynein 1 light intermediate -
The Regulatory Roles of Phosphatases in Cancer
Oncogene (2014) 33, 939–953 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc REVIEW The regulatory roles of phosphatases in cancer J Stebbing1, LC Lit1, H Zhang, RS Darrington, O Melaiu, B Rudraraju and G Giamas The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3--kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies. Oncogene (2014) 33, 939–953; doi:10.1038/onc.2013.80; published online 18 March 2013 Keywords: cancer; phosphatases; solid tumours GASTROINTESTINAL MALIGNANCIES abs in sera were significantly associated with poor survival in Oesophageal cancer advanced ESCC, suggesting that they may have a clinical utility in Loss of PTEN (phosphatase and tensin homologue deleted on ESCC screening and diagnosis.5 chromosome 10) expression in oesophageal cancer is frequent, Cao et al.6 investigated the role of protein tyrosine phosphatase, among other gene alterations characterizing this disease. Zhou non-receptor type 12 (PTPN12) in ESCC and showed that PTPN12 et al.1 found that overexpression of PTEN suppresses growth and protein expression is higher in normal para-cancerous tissues than induces apoptosis in oesophageal cancer cell lines, through in 20 ESCC tissues. -
Inhibition of Protein Phosphatase 1 Translation by Preventing JNK
Active ERK Contributes to Protein Translation by Preventing JNK-Dependent Inhibition of Protein Phosphatase 1 This information is current as Martha M. Monick, Linda S. Powers, Thomas J. Gross, of September 28, 2021. Dawn M. Flaherty, Christopher W. Barrett and Gary W. Hunninghake J Immunol 2006; 177:1636-1645; ; doi: 10.4049/jimmunol.177.3.1636 http://www.jimmunol.org/content/177/3/1636 Downloaded from References This article cites 59 articles, 43 of which you can access for free at: http://www.jimmunol.org/content/177/3/1636.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 28, 2021 *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 © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Active ERK Contributes to Protein Translation by Preventing JNK-Dependent Inhibition of Protein Phosphatase 11 Martha M. Monick,2 Linda S. Powers, Thomas J. Gross, Dawn M. Flaherty, Christopher W. -
Kinase-Inactive ZAP-70 Thymocyte Development By
An Improved Retroviral Gene Transfer Technique Demonstrates Inhibition of CD4− CD8− Thymocyte Development by Kinase-Inactive ZAP-70 This information is current as of September 23, 2021. Takehiko Sugawara, Vincenzo Di Bartolo, Tadaaki Miyazaki, Hiromitsu Nakauchi, Oreste Acuto and Yousuke Takahama J Immunol 1998; 161:2888-2894; ; http://www.jimmunol.org/content/161/6/2888 Downloaded from References This article cites 49 articles, 28 of which you can access for free at: http://www.jimmunol.org/content/161/6/2888.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 23, 2021 *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 © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. An Improved Retroviral Gene Transfer Technique Demonstrates Inhibition of CD42CD82 Thymocyte Development by Kinase-Inactive ZAP-701 Takehiko Sugawara,* Vincenzo Di Bartolo,§ Tadaaki Miyazaki,‡ Hiromitsu Nakauchi,* Oreste Acuto,§ and Yousuke Takahama2*† ZAP-70 is a Syk family tyrosine kinase that plays an essential role in initiating TCR signals. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
A-Kinase Anchoring Protein–Calcineurin Signaling in Long-Term Depression of Gabaergic Synapses
2650 • The Journal of Neuroscience, February 6, 2013 • 33(6):2650–2660 Cellular/Molecular A-Kinase Anchoring Protein–Calcineurin Signaling in Long-Term Depression of GABAergic Synapses Matthieu Dacher, Shawn Gouty, Steven Dash, Brian M. Cox, and Fereshteh S. Nugent Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 The postsynaptic scaffolding A-kinase anchoring protein 79/150 (AKAP79/150) signaling complex regulates excitatory synaptic trans- mission and strength through tethering protein kinase A (PKA), PKC, and calcineurin (CaN) to the postsynaptic densities of neurons (Sanderson and Dell’Acqua, 2011), but its role in inhibitory synaptic transmission and plasticity is unknown. Using immunofluorescence and whole-cell patch-clamp recording in rat midbrain slices, we show that activation of postsynaptic D2-like family of dopamine (DA) receptor in the ventral tegmental area (VTA) induces long-term depression (LTD) of GABAergic synapses on DA neurons through an inositol triphosphate receptor-mediated local rise in postsynaptic Ca 2ϩ and CaN activation accompanied by PKA inhibition, which requires AKAP150 as a bridging signaling molecule. Our data also illuminate a requirement for a clathrin-mediated internalization of GABAA receptors in expression of LTDGABA. Moreover, disruption of AKAP–PKA anchoring does not affect glutamatergic synapses onto DA neurons, suggesting that the PKA–AKAP–CaN complex is uniquely situated at GABAA receptor synapses in VTA DA neurons to regulate plasticity associated with GABAA receptors. Drug-induced modulation of GABAergic plasticity in the VTA through such novel signaling mechanisms has the potential to persistently alter the output of individual DA neurons and of the VTA, which may contribute to the reinforcing or addictive properties of drugs of abuse. -
Glycogen Degradation
Chapter 12 – Gluconeogenesis, the Pentose Phosphate Pathway and Glycogen Metabolism GLYCOGEN METABOLISM Glycogen stored in muscle and liver cells. Important in maintaining blood glucose levels. Glycogen structure: 1,4 glycosidic linkages with 1,6 branches. Branches give multiple free ends for quicker breakdown or for more places to add additional units. Glycogen Degradation Glucose residues of starch and glycogen released through enzymes called starch phosphorylases and glycogen phosphorylases. Catalyze phosphorolosis: polysaccharide +Pi ---> polysaccharide(n-1) + glucose 1-phosphate Pyridoxal phosphate (PLP) is prosthetic group in active site of enzyme; serves as a proton donor in active site. Allosterically inhibited by high [ATP] and high [glucose 6-phosphate]. Allosterically activated by high [AMP]. Sequentially removes glucose residues from nonreducing ends of glycogen, but stops 4 glucose residues from branch point --> leaves a limit dextran. Limit dextran further degraded by glycogen-debranching enzyme (glucanotransferase activity) which relocated the chain to a free hydroxyl end. Amylo-1,6-glucosidase activity of debranching enzyme removes remaining residues of chain. This leaves substrate for glycogen phosphorylase. Each glucose molecule released from glycogen by debranching enzyme will yield 3 ATPs in glycolysis. Each glucose molecule released by glycogen phosphorylase will yield 2 ATPs in glycolysis. Why? . ATP not needed in first step because glucose 1-phosphate already formed. phosphoglucomutase glucose 1-phosphate ----------------------> glucose 6-phosphate 1) In liver, kidney, pancreas, small intestine, glucose 6-phosphatase glucose 6-phosphate --------------------------> glucose + Pi 2 Glycogen Synthesis Not reverse of glycogen degradation because different enzymes are used. About 2/3 of glucose ingested during a meal is converted to glycogen.