Current Views on the Interplay Between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia
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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. -
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Protein Tyrosine Phosphatase Receptor Type γ Is a JAK Phosphatase and Negatively Regulates Leukocyte Integrin Activation This information is current as Michela Mirenda, Lara Toffali, Alessio Montresor, Giovanni of October 1, 2021. Scardoni, Claudio Sorio and Carlo Laudanna J Immunol 2015; 194:2168-2179; Prepublished online 26 January 2015; doi: 10.4049/jimmunol.1401841 http://www.jimmunol.org/content/194/5/2168 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2015/01/23/jimmunol.140184 Material 1.DCSupplemental http://www.jimmunol.org/ References This article cites 46 articles, 16 of which you can access for free at: http://www.jimmunol.org/content/194/5/2168.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • 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 © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Protein Tyrosine Phosphatase Receptor Type g Is a JAK Phosphatase and Negatively Regulates Leukocyte Integrin Activation Michela Mirenda,* Lara Toffali,*,† Alessio Montresor,*,† Giovanni Scardoni,† Claudio Sorio,* and Carlo Laudanna*,† Regulation of signal transduction networks depends on protein kinase and phosphatase activities. -
A Homozygous Deletion Within the Carbonic Anhydrase-Like Domain of the Ptprg Gene in Murine L-Cells1
(CANCER RESEARCH 53. 14«)»-1502.April1. 1993| Advances in Brief A Homozygous Deletion within the Carbonic Anhydrase-like Domain of the Ptprg Gene in Murine L-Cells1 Kishore K. Wary, Zhuangwei Lou, Arthur M. Buchberg, Linda D. Siracusa, Teresa Druck, Sal LaForgia, and Kay Huebner2 Jefferson Cancer Instilare. Thomas Jefferson Medical College, Philadelphia. Pennsylvania ¡9ÃŒ07 Abstract and murine predicted amino acid sequences for this isoform are greater than 90% identical: the Ptprg gene contains a single trans- Protein tyrosine phosphatases, on purely theoretical grounds, were sug membrane domain and two tandem tyrosine phosphatase domains. gested as possible tumor suppressor genes, and receptor protein tyrosine The extracellular region contains one fibronectin type repeat and. like phosphatase 7 (PTPRG ) has been proposed, on the basis of its location at the PTPRZ gene (7).' an NH2-terminal region of 266 amino acids with human chromosome region 3pl4.2, specifically as a tumor suppressor gene —¿30%sequence similarity to members of the carbonic anhydrase for renal cell carcinoma. We have isolated murine genomic and complementary DNA clones for enzyme family (8). analysis and mapping of the murine Ptprg locus; interspecific backcross During an investigation of the genomic organization of human and analysis showed that the Ptprg locus maps to the centramene region of mouse Ptprg loci, we noted extensive polymorphism of the murine mouse chromosome 14. We also observed a homozygous, intragenic dele PÃprglocus5 and a homozygous deletion of a portion of the CA-like tion in the Ptprg gene in all donai derivatives of the original I.-cell strain, domain in murine L-cell lines, which we undertook to describe in a methylcholanthrene-treated mouse connective tissue cell line which pro detail, since homozygous deletion of a gene is one of the hallmarks of duces sarcomas in syngeneic mice. -
Supplementary Data
Progressive Disease Signature Upregulated probes with progressive disease U133Plus2 ID Gene Symbol Gene Name 239673_at NR3C2 nuclear receptor subfamily 3, group C, member 2 228994_at CCDC24 coiled-coil domain containing 24 1562245_a_at ZNF578 zinc finger protein 578 234224_at PTPRG protein tyrosine phosphatase, receptor type, G 219173_at NA NA 218613_at PSD3 pleckstrin and Sec7 domain containing 3 236167_at TNS3 tensin 3 1562244_at ZNF578 zinc finger protein 578 221909_at RNFT2 ring finger protein, transmembrane 2 1552732_at ABRA actin-binding Rho activating protein 59375_at MYO15B myosin XVB pseudogene 203633_at CPT1A carnitine palmitoyltransferase 1A (liver) 1563120_at NA NA 1560098_at AKR1C2 aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 2; bile acid binding pro 238576_at NA NA 202283_at SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), m 214248_s_at TRIM2 tripartite motif-containing 2 204766_s_at NUDT1 nudix (nucleoside diphosphate linked moiety X)-type motif 1 242308_at MCOLN3 mucolipin 3 1569154_a_at NA NA 228171_s_at PLEKHG4 pleckstrin homology domain containing, family G (with RhoGef domain) member 4 1552587_at CNBD1 cyclic nucleotide binding domain containing 1 220705_s_at ADAMTS7 ADAM metallopeptidase with thrombospondin type 1 motif, 7 232332_at RP13-347D8.3 KIAA1210 protein 1553618_at TRIM43 tripartite motif-containing 43 209369_at ANXA3 annexin A3 243143_at FAM24A family with sequence similarity 24, member A 234742_at SIRPG signal-regulatory protein gamma -
(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. -
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 ........................................................................................ -
Supplementary Table 2
Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942 -
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. -
Receptor Protein Tyrosine Phosphatases Control Purkinje Neuron Firing
Receptor protein tyrosine phosphatases control Purkinje neuron firing Alexander S. Brown1, Pratap Meera2, Gabe Quinones1, Jessica Magri1, Thomas S. Otis3, Stefan M. Pulst4, and Anthony E. Oro1,5 1Program in Epithelial Biology Stanford University School of Medicine, Stanford CA, 2Department of Neurobiology University of California Los Angeles, Los Angeles CA 3Sainsbury Wellcome Centre for Neural Circuits and Behavior, University College London, London, United Kingdom 4Department of Neurology, University of Utah Medical Center, Salt Lake City, UT 5To whom correspondence should be addressed: Anthony E.Oro ( [email protected]) . Abstract (173/200 words): Spinocerebellar ataxias (SCA) are a genetically heterogeneous family of cerebellar neurodegenerative diseases characterized by abnormal firing of Purkinje neurons and degeneration. We recently demonstrated the slowed firing rates seen in several SCAs share a common etiology of hyper-activation of the Src family of non-receptor tyrosine kinases (SFKs)1. However, because of the lack of effective neuroactive, clinically available SFK inhibitors, alternative mechanisms to modulate SFK activity are needed. Previous studies demonstrate that SFK activity can be enhanced by the removal of inhibitory phospho-marks by receptor-protein-tyrosine phosphatases (RPTPs)2,3. In this Extra View we show that MTSS1 inhibits SFK activity through the binding and inhibition of a subset of the RPTP family members. RPTP activity normally results in SFK activation in vitro, and lowering RPTP activity in cerebellar slices using recently described RPTP peptide inhibitors increases the suppressed Purkinje neuron basal firing rates seen in two different SCA models. Together these results identify RPTPs as novel effectors of cerebellar activity, extending the MTSS1/SFK regulatory circuit we previously described and expanding the therapeutic targets for SCA patients. -
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. -
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. -
Lipid Phosphatases Identified by Screening a Mouse Phosphatase Shrna Library Regulate T-Cell Differentiation and Protein Kinase
Lipid phosphatases identified by screening a mouse PNAS PLUS phosphatase shRNA library regulate T-cell differentiation and Protein kinase B AKT signaling Liying Guoa, Craig Martensb, Daniel Brunob, Stephen F. Porcellab, Hidehiro Yamanea, Stephane M. Caucheteuxa, Jinfang Zhuc, and William E. Paula,1 aCytokine Biology Unit, cMolecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and bGenomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840 Contributed by William E. Paul, March 27, 2013 (sent for review December 18, 2012) Screening a complete mouse phosphatase lentiviral shRNA library production (10, 11). Conversely, constitutive expression of active using high-throughput sequencing revealed several phosphatases AKT leads to increased proliferation and enhanced Th1/Th2 cy- that regulate CD4 T-cell differentiation. We concentrated on two lipid tokine production (12). phosphatases, the myotubularin-related protein (MTMR)9 and -7. The amount of PI[3,4,5]P3 and the level of AKT activation are Silencing MTMR9 by shRNA or siRNA resulted in enhanced T-helper tightly controlled by several mechanisms, including breakdown of (Th)1 differentiation and increased Th1 protein kinase B (PKB)/AKT PI[3,4,5]P3, down-regulation of the amount and activity of PI3K, phosphorylation while silencing MTMR7 caused increased Th2 and and the dephosphorylation of AKT (13). PTEN is a major negative Th17 differentiation and increased AKT phosphorylation in these regulator of PI[3,4,5]P3. It removes the 3-phosphate from the cells.