DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb USOO766277OB2 (12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb. 16, 2010 (54) LOW MOLECULARWEIGHT PROTEIN WO WOO1? 12172 A1 2, 2001 TYROSINE PHOSPHATASE (LMW-PTP) ASA WO WO 01/12840 A2 2, 2001 DAGNOSTIC AND THERAPEUTIC TARGET WO WOO3,O94859 A2 11/2003 WO WOO3,O993 13 A1 12/2003 75 WO WO 2004/O14292 A2 2, 2004 (75) Inventor: Michael S. Kinch, Laytonville, MD WO WO 2004/O14292 A3 2, 2004 WO WO 2005/051307 A2 6, 2005 (73) Assignee: Purdue Research Foundation, West W W SE A. 3. LaFayette, IN (US) WO WO 2005/055948 A3 6, 2005 - WO WO 2005/056766 A2 6, 2005 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 350 days. Carles-Kinchet al., “Antibody targeting of the EphA2tyrosine kinase inhibits malignant cell behavior.” May 15, 2002 Cancer Research (21) Appl. No.: 10/515,358 62(10):2840-2847. Parket al., “Low-molecular-weight protein tyrosine phosphatase is a (22) PCT Filed: May 22, 2003 positive component of the fibroblast growth factor receptor signaling pathway.” May 15, 2002 Molecular and Cellular Biology (86). PCT No.: PCT/USO3A16269 22(10):3404-3414. Souza et al., “From immune response to cancer: a spot on the low S371 (c)(1), molecular weight protein tyrosine phosphatase.” Apr. 2009 Cellular (2), (4) Date: Aug. 11, 2005 and Molecular Life Sciences 66(6):1140-1153. Available online on Nov. 11, 2008. (87) PCT Pub. No.: WO03/0993 13 Supplementary European Search Report mailed Jun. 8, 2009, for EP Application No. 03734142.7 (3 pgs). PCT Pub. Date: Dec. 4, 2003 Cann, "Genetic clues to dispersal in human populations: retracting the past from the present.” Mar. 2, 2001 Science 291: 1742-1748. O O Garcia-Closas et al., “Collection of genomic DNA from adults in (65) Prior Publication Data epidemiological studies by buccal cytobrush and mouthwash.” Jun. US 2006/0093608A1 May 4, 2006 2001 Cancer Epidemiology, Biomarkers & Prevention 10:687-696. National Center for Biotechnology Information, National Library of Related U.S. Application Data Medicine, National Institutes of Health. GenBank Locus NM 007099, Accession No. NM 007099, Version NM 007099.1 (60) Provisional application No. 60/382.988, filed on May GI:6005987, "Homo sapiens acid phophatase 1, soluble (ACP1), 23, 2002. transport variant b, mRNA. online). Bethesda, MD retrieved on Mar. 26, 2008). Retrieved from the Internet: <http://www.ncbi.nlm. (51) Int. Cl. nih.gov/entrez/viewer.fcgi?6005987:OLD12:5701672; 3 pgs. A6 IK 38/00 (2006.01) National Center for Biotechnology Information, National Library of (52) U.S. Cl. .......................................................... 5142 Medicine, National Institutes of Health, GenPept Locus P24666, Accession No. P24666, Version P24666 GI: 1709543, “Red cell acid (58) Field of Classification Search ............... ... 514/2 phosphatase 1, isoenzyme F (ACP1) (Low molecular weight See application file for complete search history. phosphotyrosine phosphatase) (Adipocyte acid phosphatase, isoenzyme alpha).” online). Bethesda. MD retrieved on Mar. 25. (56) References Cited 2008. Retrieved from the Internet: <http://www.ncbi.nlm.nih.gov/ U.S. PATENT DOCUMENTS entrez/viewer.fcgi? 1709543:OLD11:669086>; 4pgs. Akerud et al., “Intramolecular Dynamics of Low Molecular Weight 5,876,949 A 3/1999 Dreyfuss et al. Protein Tyrosine Phosphatase in Monomer-Dimer Equilibrium Stud 5,958,957 A 9, 1999 Andersen et al. ied by NMR: A Model for Changes in Dynamics Upon Target Bind 6,927,203 B1 8, 2005 Kinch et al. ing.” J. Mol. Biol. Sep. 6, 2002; 322(1):137-152. 7,101,976 B1 9/2006 Kilpatricket al. 7,192,698 B1 3/2007 Kinch et al. (Continued) 7,479,368 B2 1/2009 Brown et al. 7,485.420 B2 2/2009 Markowitz Primary Examiner Christopher HYaen 7,507,418 B2 3/2009 Atkinson et al. (74) Attorney, Agent, or Firm Mueting Raasch & Gebhardt, 2004/0028685 A1 2/2004 Kinch et al. P.A. 2004/009 1486 A1 5, 2004 Kinch et al. (57) ABSTRACT 2005, 0147593 A1 7, 2005 Kinch 2005. O152899 A1 7, 2005 Kinch et al. Low molecular weight protein tyrosine phosphatase (LMW 2005. O153923 A1 7, 2005 Kinch PTP) is identified as a novel diagnostic and therapeutic target 2005, 0169931 A1 8, 2005 Kinch et al. in cancer diagnosis, prognosis and treatment. The invention 2006, OO88541 A1 4/2006 Kinch et al. 2006/0093608 A1 5, 2006 Kinch provides diagnostic and treatment methods useful in connec 2007, OO86943 A1 4/2007 Kinch et al. tion with cancers expressing LMW-PTP and, optionally, 2008.00899.31 A1 4, 2008 Kinch EphA2 receptor. Also provided is a screening method that utilizes changes in the amount and/or activity of LMW-PTP FOREIGN PATENT DOCUMENTS to identify candidate cancer therapeutic agents that effec tively target the oncoprotein EphA2. EP 1242060 B1 5, 2006 EP 16957 O2 A2 8, 2006 15 Claims, 22 Drawing Sheets US 7,662,770 B2 Page 2 OTHER PUBLICATIONS Gilardi-Hebenstreitet al., “An Eph-related Receptor Protein Tyrosine Kinase Gene Segmentally Expressed in the Developing Mouse Andres et al., “Expression of Two Novel eph-related Receptor Pro Hindbrain.” Oncogene, Dec. 1992;7(12):2499-2506. tein Tyrosine Kinases in Mammary Gland Development and Gustafson et al., “Solution Structure of the Low Molecular Weight Carcinogenesis.” Oncogene, May 1994:9: 1461-1467. Protein Tyrosine Phosphatase From Tritrichomonas foetus Reveals a Arakawa et al., “Genomic Organization of the Klebsiella Flexible Phosphate Binding Loop.” Protein Sci., Oct. 2005; pneumoniae cps Region Responsible for Serotype K2 Capsular 14(10):2515-2525. Polysaccharide Synthesis in the Virulent Strain Chedid.” J. Heinrikson, "Purification and Characterization of a Low Molecular Bacteriol. Apr. 1995; 177(7):1788-1796. Available online at Journal Weight Acid Phosphatase from Bovine Liver.” J. Biol. Chem. of Bacteriology retrieved Oct. 25, 2006). Retrieved from the 1969:244(2):299-307. Available online at JBC Online retrieved Oct. Internet:<URL:http://b.asm.org/cgi/reprint/177/7/1788>; 9 pgs. 25, 2006). Retrieved from the Internet:<URL:http://www.jbc.org/ Boivin et al., “The Human Red Cell Acid Phosphatase Is a cgi/reprint/244/2/299>; 9 pgs. Phosphotyrosine Protein Phosphatase Which Dephosphorylates the Hesset al., “Molecular Regulation of Tumor Cell Vasculogenic Mim Membrane ProteinBand 3.” Biochem. Biophys. Res. Commmun., Jan. icry by Tyrosine Phosphorylation: Role of Epithelial Cell Kinase 29, 1986; 134(2):557-564. (Eck/EphA2).” Cancer Res, Apr. 15, 2001:61(8):3250-3255. Bugert et al., “Characterization of the aims 1 Gene Product as a Low Hirai et al., “A Novel Putative Tyrosine Kinase Receptor Encoded by Molecular Weight Acid Phosphatase Controlling Exopolysaccharide the eph Gene.” Science, Dec. 18, 1987:238(4834): 1717-1720. Synthesis of Erwinia amylovora,” FEBS Lett., Jan. 1997:400(2):252 Huang et al., “HCPTPA, a Protein Tyrosine Phosphatase That Regu 256. lates Vascular Endothelial Growth Factor Receptor-Mediated Signal Brackenbury, “Control of Carcinoma Cell Motility by E-Cadherin.” Transduction and Biological Activity.” J. Biol. Chem. Dec. 31. Abstract and Final Report, Grant No. DAMD 17-98-1-8292; United 1999:274(53):38183-38188. States Army Medical Research and Material Command Grant, Jacob et al., “A Receptor Tyrosine Kinase, UFO/Axl, and Other project dates Aug. 1, 1998 to Jul. 31, 2002 retrieved on Jun. 7, 2007). Genes Isolated by a Modified Differential Display PCR Are Retrieved from the Internet:<URL:http://stinet.dtic.mil/oai?oai? Overexpressed in Metastatic Prostatic Carcinoma Cell Line DU145.” &verb-getRecord&metadataPrefix=html Cancer Detect Prev., 1999:23(4):325-332. &identifier=ADA409404; 31 pgs. Kikawa et al., “Regulation of the EphA2 Kinase by the Low Molecu Caselli et al., “The Inactivation Mechanism of Low Molecular lar Weight Tyrosine Phosphatase Induces Transformation.” J. Biol. Weight Phosphotyrosine-protein Phosphatase by H.O.” J. Biol. Chem. Oct. 18, 2002:277(42):39274-39279; electronically pub Chem. Dec. 4, 1998; 273(49): 32554-32560. Available online at JBC lished Aug. 6, 2002. Online retrieved Oct. 25, 2006. Retrieved from the Kinch et al., “Tyrosine Phosphorylation Regulates the Adhesions of Internet:<URL:http://www.jbc.org/cgi/reprint/273/49/325542; 7 Ras-Transformed Breast Epithelia.” J. Cell Biol. Jul. pg.S. 1995; 130(2):461-471. Chernoff et al., “A Major Phosphotyrosyl-Protein Phosphatase from Kinch, Michael, “EphA2—A Marker of Breast Cancer Progression.” Bovine Heart is Associated with a Low-Molecular-Weight Acid Grant Abstract, Grant No. 5R21CA85615-02 online. National Can Phosphatase.” Arch. Biochem. Biophy's. Jul. 1985:240(1):135-145. cer Institute, project dates Apr. 1, 2000 to Mar. 31, 2002 retrieved Chiaraugi et al., “The Src and Signal Transducers and Activators of Sep. 22, 2006). Retrieved from the Internet:<URL:http://crisp.cit. Transcription Pathways. As Specific Targets for Low Molecular nih.gov/>; 2 pgs. Weight Phosphotyrosine-protein Phosphatase in Platelet-derived Kinch et al., “Overexpression and Functional Alterations of the Growth Factor Signaling.” J. Biol. Chem. Mar. 20. EphA2 Tyrosine Kinase in Cancer.” Clin. Exp. Metastasis, 1998:273(12):6776-6785. 2003:20(1):59-68. Clarket al., “Overexpression of the Ras-related TC21/R-Ras2 Pro Kinch et al., “Predictive Value of the EphA2 Receptor Tyrosine tein May Contribute to the Development of Human Breast Cancers.” Kinase in Lung Cancer Recurrence and Survival.” Clin. Cancer Res., Oncogene, 1996 12(1): 169-176. Feb. 2003:9(2):613-618. Corden et al. “Low Molecular Weight Phosphatase.” Abstract, p. 20 Lindberg et al., “cDNA Cloning and Characterization of eck, an of Project Detail, General Basic Research in the Walther Cancer Epithelial Cell Receptor Protein-Tyrosine Kinase in the eph/elk Fam Center of Excellence online).
Load more

Recommended publications
  • Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
    Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................
    [Show full text]
  • Figure S1. Reverse Transcription‑Quantitative PCR Analysis of ETV5 Mrna Expression Levels in Parental and ETV5 Stable Transfectants
    Figure S1. Reverse transcription‑quantitative PCR analysis of ETV5 mRNA expression levels in parental and ETV5 stable transfectants. (A) Hec1a and Hec1a‑ETV5 EC cell lines; (B) Ishikawa and Ishikawa‑ETV5 EC cell lines. **P<0.005, unpaired Student's t‑test. EC, endometrial cancer; ETV5, ETS variant transcription factor 5. Figure S2. Survival analysis of sample clusters 1‑4. Kaplan Meier graphs for (A) recurrence‑free and (B) overall survival. Survival curves were constructed using the Kaplan‑Meier method, and differences between sample cluster curves were analyzed by log‑rank test. Figure S3. ROC analysis of hub genes. For each gene, ROC curve (left) and mRNA expression levels (right) in control (n=35) and tumor (n=545) samples from The Cancer Genome Atlas Uterine Corpus Endometrioid Cancer cohort are shown. mRNA levels are expressed as Log2(x+1), where ‘x’ is the RSEM normalized expression value. ROC, receiver operating characteristic. Table SI. Clinicopathological characteristics of the GSE17025 dataset. Characteristic n % Atrophic endometrium 12 (postmenopausal) (Control group) Tumor stage I 91 100 Histology Endometrioid adenocarcinoma 79 86.81 Papillary serous 12 13.19 Histological grade Grade 1 30 32.97 Grade 2 36 39.56 Grade 3 25 27.47 Myometrial invasiona Superficial (<50%) 67 74.44 Deep (>50%) 23 25.56 aMyometrial invasion information was available for 90 of 91 tumor samples. Table SII. Clinicopathological characteristics of The Cancer Genome Atlas Uterine Corpus Endometrioid Cancer dataset. Characteristic n % Solid tissue normal 16 Tumor samples Stagea I 226 68.278 II 19 5.740 III 70 21.148 IV 16 4.834 Histology Endometrioid 271 81.381 Mixed 10 3.003 Serous 52 15.616 Histological grade Grade 1 78 23.423 Grade 2 91 27.327 Grade 3 164 49.249 Molecular subtypeb POLE 17 7.328 MSI 65 28.017 CN Low 90 38.793 CN High 60 25.862 CN, copy number; MSI, microsatellite instability; POLE, DNA polymerase ε.
    [Show full text]
  • Journal of Gynecology & Obstetrics Cytosolic Low Molecular Weight
    Journal of Gynecology & Obstetrics Case Report Open Access Association with ACP1 genotypes has been observed in immune Cytosolic Low Molecular Weight disorders such as T1D, Chron’s disease and allergy [10-12]. Protein Tyrosine Phosphatase In the present paper we have investigated a possible effect of high activity ACP1 genotypes on some clinical manifestations of and Clinical Manifestations of endometriosis. Endometriosis Material & Methods We have studied 113 women from the White population of Fulvia Gloria-Bottini*, Adalgisa Pietropolli, Anna Neri, Andrea Rome admitted consecutively to the Hospital with the diagnosis of Magrini and Egidio Bottini Department of Biomedicine and Prevention, University of Rome Tor Vergata, endometriosis. The disease was diagnosed during laparoscopy and the Rome, Italy criteria for the inclusion in the study were those proposed by Holt and Weiss [13]. All subjects gave verbal informed consent to partecipate in *Corresponding author: Fulvia Gloria-Bottini, Email: [email protected] the study that was approved by the Council of Department. Received: 28 October 2016; Accepted: 26 December 2016; Published: 06 January 2017 Controls were blood donors without manifestation of endometriosis. ACP1 genotye was determined by DNA analysis as previously Abstract described [12]. Chi square test of Independence and Odds Ratio analysis were carried out by SPSS programs [14]. We have previously observed that high activity ACP1 (Acid Phosphatase locus 1) genotypes are more frequent in endometriosis. The number of subjects is not the same for all clinical manifestations considered due to lack of reliable information for some manifestations. ACP1 encodes for cytosolic Low Molecular Weight Protein Tyrosine Phosphatase (cLMWPTP), an enzyme present in all tissue that is composed by two isoforms that have different biochemical properties, Results different concentration among genotypes and probably different Table 2 shows the proportion of high activity *C/*A and *C/*B functions in the cell.
    [Show full text]
  • Current Views on the Interplay Between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia
    cancers Review Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia Christian Boni and Claudio Sorio * Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-045-802-7688 Simple Summary: The chromosomal alteration t(9;22) generating the BCR-ABL1 fusion protein represents the principal feature that distinguishes some types of leukemia. An increasing number of articles have focused the attention on the relevance of protein phosphatases and their potential role in the control of BCR-ABL1-dependent or -independent signaling in different areas related to the biology of chronic myeloid leukemia. Herein, we discuss how tyrosine and serine/threonine protein phosphatases may interact with protein kinases, in order to regulate proliferative signal cascades, quiescence and self-renewals on leukemic stem cells, and drug-resistance, indicating how BCR-ABL1 can (directly or indirectly) affect these critical cells behaviors. We provide an updated review of the literature on the function of protein phosphatases and their regulation mechanism in chronic myeloid leukemia. Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by BCR- ABL1 oncogene expression. This dysregulated protein-tyrosine kinase (PTK) is known as the principal driver of the disease and is targeted by tyrosine kinase inhibitors (TKIs). Extensive documentation has Citation: Boni, C.; Sorio, C. Current elucidated how the transformation of malignant cells is characterized by multiple genetic/epigenetic Views on the Interplay between changes leading to the loss of tumor-suppressor genes function or proto-oncogenes expression. Tyrosine Kinases and Phosphatases in The impairment of adequate levels of substrates phosphorylation, thus affecting the balance PTKs Chronic Myeloid Leukemia.
    [Show full text]
  • The Role of Protein-Tyrosine Phosphatases for Sensitivity and Resistance of CML-Cells to Tyrosine-Kinase Inhibitors
    The role of protein-tyrosine phosphatases for sensitivity and resistance of CML-cells to tyrosine-kinase inhibitors Dissertation zur Erlangung des akademischen Grades „doctor rerum naturalium“ (Dr. rer. nat.) vorgelegt dem Rat der Fakultät für Biowissenschaften der Friedrich-Schiller-Universität Jena von Diplom Biochemikerin Julia Drube geboren am 23. November 1982 in Trier Tag der öffentlichen Verteidigung 29.05.2018 Gutachter 1. apl. Prof. Dr. Frank-Dietmar Böhmer (Jena, Deutschland) 2. PD Dr. Christian Kosan (Jena, Deutschland) 3. Prof. Dr. Wiljan J. A. J. Hendriks (Nijmegen, Niederlande) I Zusammenfassung Die Chronisch myeloische Leukämie (CML) ist eine Krankheit des hämatopoetischen Systems, welche durch die Expression von BCR-ABL1 ausgelöst wird. Dieses Onkoprotein ist eine konstitutiv aktive Protein-Tyrosinkinase (PTK), welche in Zellen Signalwege anschaltet, die unkontrolliertes Wachstum und Überleben steuern. Aus diesem Grund kann die CML mit spezifischen Tyrosinkinase-Inhibitoren (TKI) behandelt werden, die die Funktion von BCR-ABL1 hemmen. Imatinib, der erste TKI der in der Klinik Anwendung fand, hat die Therapie der CML revolutioniert: Die Patienten hatten gute Ansprechraten und viele ein gutes Langzeitüberleben mit vergleichsweise wenig Nebenwirkungen. Die Einführung von Nilotinib, eines noch potenteren Zweit-Generationen-TKI führte zu einem weiter verbesserten Wirkprofil mit schnellerem und tieferem Ansprechen. Ein Teil der Patienten wird voraussichtlich die Therapie absetzen können und trotzdem in therapiefreier Remission bleiben. Gegenstand aktueller klinischen Studien ist die Optimierung der Therapie und die genauere Untersuchung der Voraussetzungen für ein erfolgreiches Absetzen der TKI. Es ist bereits bekannt, dass ein besonders schnelles Erreichen einer anhaltenden, tiefen molekularen Remission sich günstig auf eine funktionelle Heilung auswirkt. Aus diesem Grund ist es von großem Interesse, die molekularen Mechanismen besser zu verstehen, welche das Erreichen der tiefen molekularen Remission beeinflussen.
    [Show full text]
  • Live-Cell Imaging Rnai Screen Identifies PP2A–B55α and Importin-Β1 As Key Mitotic Exit Regulators in Human Cells
    LETTERS Live-cell imaging RNAi screen identifies PP2A–B55α and importin-β1 as key mitotic exit regulators in human cells Michael H. A. Schmitz1,2,3, Michael Held1,2, Veerle Janssens4, James R. A. Hutchins5, Otto Hudecz6, Elitsa Ivanova4, Jozef Goris4, Laura Trinkle-Mulcahy7, Angus I. Lamond8, Ina Poser9, Anthony A. Hyman9, Karl Mechtler5,6, Jan-Michael Peters5 and Daniel W. Gerlich1,2,10 When vertebrate cells exit mitosis various cellular structures can contribute to Cdk1 substrate dephosphorylation during vertebrate are re-organized to build functional interphase cells1. This mitotic exit, whereas Ca2+-triggered mitotic exit in cytostatic-factor- depends on Cdk1 (cyclin dependent kinase 1) inactivation arrested egg extracts depends on calcineurin12,13. Early genetic studies in and subsequent dephosphorylation of its substrates2–4. Drosophila melanogaster 14,15 and Aspergillus nidulans16 reported defects Members of the protein phosphatase 1 and 2A (PP1 and in late mitosis of PP1 and PP2A mutants. However, the assays used in PP2A) families can dephosphorylate Cdk1 substrates in these studies were not specific for mitotic exit because they scored pro- biochemical extracts during mitotic exit5,6, but how this relates metaphase arrest or anaphase chromosome bridges, which can result to postmitotic reassembly of interphase structures in intact from defects in early mitosis. cells is not known. Here, we use a live-cell imaging assay and Intracellular targeting of Ser/Thr phosphatase complexes to specific RNAi knockdown to screen a genome-wide library of protein substrates is mediated by a diverse range of regulatory and targeting phosphatases for mitotic exit functions in human cells. We subunits that associate with a small group of catalytic subunits3,4,17.
    [Show full text]
  • Phosphatases Page 1
    Phosphatases esiRNA ID Gene Name Gene Description Ensembl ID HU-05948-1 ACP1 acid phosphatase 1, soluble ENSG00000143727 HU-01870-1 ACP2 acid phosphatase 2, lysosomal ENSG00000134575 HU-05292-1 ACP5 acid phosphatase 5, tartrate resistant ENSG00000102575 HU-02655-1 ACP6 acid phosphatase 6, lysophosphatidic ENSG00000162836 HU-13465-1 ACPL2 acid phosphatase-like 2 ENSG00000155893 HU-06716-1 ACPP acid phosphatase, prostate ENSG00000014257 HU-15218-1 ACPT acid phosphatase, testicular ENSG00000142513 HU-09496-1 ACYP1 acylphosphatase 1, erythrocyte (common) type ENSG00000119640 HU-04746-1 ALPL alkaline phosphatase, liver ENSG00000162551 HU-14729-1 ALPP alkaline phosphatase, placental ENSG00000163283 HU-14729-1 ALPP alkaline phosphatase, placental ENSG00000163283 HU-14729-1 ALPPL2 alkaline phosphatase, placental-like 2 ENSG00000163286 HU-07767-1 BPGM 2,3-bisphosphoglycerate mutase ENSG00000172331 HU-06476-1 BPNT1 3'(2'), 5'-bisphosphate nucleotidase 1 ENSG00000162813 HU-09086-1 CANT1 calcium activated nucleotidase 1 ENSG00000171302 HU-03115-1 CCDC155 coiled-coil domain containing 155 ENSG00000161609 HU-09022-1 CDC14A CDC14 cell division cycle 14 homolog A (S. cerevisiae) ENSG00000079335 HU-11533-1 CDC14B CDC14 cell division cycle 14 homolog B (S. cerevisiae) ENSG00000081377 HU-06323-1 CDC25A cell division cycle 25 homolog A (S. pombe) ENSG00000164045 HU-07288-1 CDC25B cell division cycle 25 homolog B (S. pombe) ENSG00000101224 HU-06033-1 CDKN3 cyclin-dependent kinase inhibitor 3 ENSG00000100526 HU-02274-1 CTDSP1 CTD (carboxy-terminal domain,
    [Show full text]
  • Gene Co-Expression Network Analysis in Human Spinal Cord Highlights Mechanisms 2 Underlying Amyotrophic Lateral Sclerosis Susceptibility 3 4 Jerry C
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.16.253377; this version posted August 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Gene co-expression network analysis in human spinal cord highlights mechanisms 2 underlying amyotrophic lateral sclerosis susceptibility 3 4 Jerry C. Wang1, Gokul Ramaswami1, Daniel H. Geschwind1,2,3,* 5 6 Affiliations 7 1 Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, 8 University of California, Los Angeles, Los Angeles, CA, United States of America 9 10 2 Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, 11 University of California, Los Angeles, Los Angeles, CA, United States of America 12 13 3 Department of Human Genetics, David Geffen School of Medicine, University of California, Los 14 Angeles, Los Angeles, CA, United States of America 15 16 *. Correspondence should be addressed to D.H.G: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.08.16.253377; this version posted August 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 17 Abstract 18 Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease defined by motor neuron 19 (MN) loss.
    [Show full text]
  • Inhibition of Dual-Specificity Phosphatase 26 by Ethyl-3,4-Dephostatin: Ethyl-3,4-Dephostatin As a Multiphosphatase Inhibitor
    ORIGINAL ARTICLES College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea Inhibition of dual-specificity phosphatase 26 by ethyl-3,4-dephostatin: Ethyl-3,4-dephostatin as a multiphosphatase inhibitor HUIYUN SEO, SAYEON CHO Received September 30, 2015, accepted November 6, 2015 Sayeon Cho, Ph.D., College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea [email protected] Pharmazie 71: 196–200 (2016) doi: 10.1691/ph.2016.5803 Protein tyrosine phosphatases (PTPs) regulate protein function by dephosphorylating phosphorylated proteins in many signaling cascades and some of them have been targets for drug development against many human diseases. There have been many reports that some chemical inhibitors could regulate particular phosphatases. However, there was no extensive study on specificity of inhibitors towardss phosphatases. We investigated the effects of ethyl-3,4-dephostatin, a potent inhibitor of five PTPs including PTP-1B and Src homology-2-containing protein tyrosine phosphatase-1 (SHP-1), on thirteen other PTPs using in vitro phosphatase assays. Of them, dual-specificity protein phosphatase 26 (DUSP26), which inhibits mitogen-activated protein kinase (MAPK) and p53 tumor suppressor and is known to be overexpressed in anaplastic thyroid carcinoma, was inhibited by ethyl- 3,4-dephostatin in a concentration-dependent manner. Kinetic studies with ethyl-3,4-dephostatin and DUSP26 revealed competitive inhibition, suggesting that ethyl-3,4-dephostatin binds to the catalytic site of DUSP26 like other substrate PTPs. Moreover, ethyl-3,4-dephostatin protects DUSP26-mediated dephosphorylation of p38, a member of the MAPK family, and p53. Taken together, these results suggest that ethyl-3,4-dephostatin functions as a multiphosphatase inhibitor and is useful as a therapeutic agent for cancers overexpressing DUSP26.
    [Show full text]
  • Target Genes Regulated by Hsa-Mir-21, by Hsa-Mir-203, by Hsa-Mir-21 and by Hsa-Mir-143
    Supplemental table 1: Target genes regulated by hsa-miR-205 Index Target gene Index Target gene Index Target gene Index Target gene Index Target gene 1 KCTD20 35 UBE2Z 69 SLC38A1 103 LPCAT1 137 STK38L 2 MAPK14 36 YWHAH 70 ANGPTL7 104 MARCKS 138 C1orf123 3 TXNL1 37 RBBP4 71 CTGF 105 MED13 139 GUCD1 4 SPDL1 38 LRP1 72 CYR61 106 IPO7 140 CDK6 5 TCF20 39 IMPAD1 73 TP73 107 PHC2 141 CDKN2AIPNL 6 RAN 40 GNAS 74 EGLN2 108 PICALM 142 CLIP1 7 RGS6 41 MED1 75 ERBB2 109 PLAGL2 143 CUL5 8 HOXA11 42 INPPL1 76 PRRG4 110 NDUFA4 144 C6orf201 9 PAPPA-AS1 43 DDX5 77 F2RL2 111 NDUFB2 145 VTI1A 10 PRR15 44 E2F1 78 GOT1 112 NIPA2 146 SLC5A12 11 ACTRT3 45 E2F5 79 NUFIP2 113 NOTCH2 147 MAML2 12 YES1 46 ZEB2 80 IL24 114 PANK1 148 MAP3K9 13 SRC 47 ERBB3 81 IL32 115 PARD6B 149 NUDT21 14 NPRL3 48 PRKCE 82 RNF217 116 TMEM66 150 DNAJA1 15 NFAT5 49 SLC41A1 83 ZNF585B 117 EZR 151 CCDC108 16 XPOT 50 SLC7A2 84 SIGMAR1 118 ENPP4 152 SHISA6 17 KCTD16 51 ZEB1 85 VEGFA 119 LRRTM4 153 ACP1 18 TMSB4X 52 PHF8 86 BCL9L 120 KCNJ10 154 BCL2 19 PLCXD2 53 TMEM201 87 CREB1 121 PHLPP2 155 NCAPG 20 TNFSF8 54 PTPRJ 88 SERINC3 122 YEATS2 156 KLHL5 21 SLC25A25 55 ETNK1 89 HMGB3 123 VAMP1 157 ACSL4 22 C11orf74 56 XPR1 90 SRD5A1 124 RTN3 158 BCL6 23 GM2A 57 MRPL44 91 PTEN 125 RFX7 159 ITGA5 24 SMNDC1 58 TM9SF2 92 ESRRG 126 RAP2B 160 ACSL1 25 BAMBI 59 PAIP2B 93 PRLR 127 TRAF3IP1 161 EID2B 26 LCOR 60 NEK9 94 ICK 128 SERTAD2 162 TEX35 27 TMEM239 61 NOX5 95 LOH12CR1 129 TOLLIP 163 YY1 28 AMOT 62 DMXL2 96 SLC39A14 130 TMEM55B 164 SMAD1 29 CDK1 63 ETF1 97 BDP1 131 TMEM123 165 SMAD4 30 SQLE 64
    [Show full text]
  • Anti-ACP1 (Ab1) (GW21548)
    3050 Spruce Street, Saint Louis, MO 63103 USA Tel: (800) 521-8956 (314) 771-5765 Fax: (800) 325-5052 (314) 771-5757 email: [email protected] Product Information Anti-ACP1 (ab1) antibody produced in chicken, affinity isolated antibody Catalog Number GW21548 Formerly listed as GenWay Catalog Number 15-288-21548, Protein-tyrosine-phosphatase, isoform 3 Antibody. – Storage Temperature Store at 20 °C The product is a clear, colorless solution in phosphate buffered saline, pH 7.2, containing 0.02% sodium azide. Synonyms: Acid phosphatase 1 isoform c, EC 3.1.3.48 Species Reactivity: Human Product Description The product of this gene belongs to the phosphotyrosine Tested Applications: WB protein phosphatase family of proteins. It functions as an Recommended Dilutions: Recommended starting dilution acid phosphatase and a protein tyrosine phosphatase by for Western blot analysis is 1:500, for tissue or cell staining hydrolyzing protein tyrosine phosphate to protein tyrosine 1:200. and orthophosphate. This enzyme also hydrolyzes ortho- phosphoric monoesters to alcohol and orthophosphate. Note: Optimal concentrations and conditions for each This protein is genetically polymorphic. and three common application should be determined by the user. alleles segregating at the corresponding locus give rise to Precautions and Disclaimer six phenotypes. Each allele appears to encode at least two This product is for R&D use only, not for drug, household, or electrophoretically different isozymes. Bf and Bs. which are other uses. Due to the sodium azide content a material produced in allele-specific ratios. Three transcript variants safety data sheet (MSDS) for this product has been sent to encoding distinct isoforms have been identified for this the attention of the safety officer of your institution.
    [Show full text]
  • Higher Intensity of Low Molecular Weight Protein Tyrosine
    Open Access Austin Biology Research Article Higher Intensity of Low Molecular Weight Protein Tyrosine Phosphatase/ ACP-1 in Survivors of Patients Diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) Compared to Non-Survivors Stanezai S1, Sahlen E1, El-Schich Z1, Fridberg M2, Fredrikson GN3, Anagnostaki L4, Tassidis H2, Abstract Persson JL5 and Wingren AG1* Adult Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous form of 1Department of Biomedical Science, Malmo University, hematopoietic cancer and difficult to treat. In order to find a better diagnostic Sweden indication for the disease, we analyzed Low Molecular Weight Protein Tyrosine 2Department of Natural Science, Kristianstad University, Phosphatase (LMWPTP) that in humans is encoded by the ACP1 gene. Sweden LMWPTP is an enzyme shown to counteract Protein Tyrosine Kinases (PTK) 3Department of Clinical Sciences Malmo, Lund and was suggested to be a negative growth factor regulator. However, the University, Sweden 18 kDa PTP can also have a positive effect on cell growth and proliferation, 4Department of Clinical Pathology, Skane University indicating a controversial role in the tumorigenic process. LMWPTP exists in Hospital, Sweden different isoforms which are electrophoretically, kinetically and immunologically 5Department of Translational Medicine, Lund University, distinct. We have studied two subgroups of DLBCL consisting of a Germinal Sweden Center B cell like (GCB) and a non-Germinal Center B cell like (non-GCB) group. *Corresponding author: Anette Gjorloff Wingren, The two subgroups have been defined by gene-expressing profiling and are Department of Biomedical Science, Health and Society, associated with differential outcome. The expression levels of LMWPTP protein Malmo University, SE20506 Malmo, Sweden was compared and showed significant differences between the GCB and non- GCB subgroups (p=0.012).
    [Show full text]