DOCSLIB.ORG

Printer-Friendly Version of PTP Classification

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Printer-Friendly Version of PTP Classification Nontransmembrane PTP subtypes (NT) Receptor–like PTP subtypes PTPOST http://ptp.cshl.edu & http://science.novonordisk.com/ptp Andersen et al Mol. Cell. Biol. 2001 Classification of the vertebrate family of PTPs into Nontransmembrane (NT) and Receptor-like subtypes (R) based on PTP domain sequence homology hPTPsigma (PTPRS) Inconsistent gene nomenclature is highlighted in red mPTPsigma (Ptprs) rPTPsigma (Ptprd) Subtypes xPTPsigma PTPsigma 0.1 826 cPTPsigma zPTPsigma xPTPdelta R2A 1000 hPTPdelta (PTPRD) PTPdelta mPTPdelta (Ptprd) xLAR hLAR (PTPRF) mLAR (Ptprf) LAR 834 rLAR (Ptprf) xPTPrho hPTPrho (PTPRT) 565 mPTPrho (Ptprt) PTPrho 668 hPTPmu (PTPRM) mPTPmu (Ptprm) PTPmu 1000 hPTPkappa (PTPRK) 712 mPTPkappa (Ptprk) PTPkappa R2B hPTPlamda (PTPRU) mPTPlamda (Ptprl) PTPlambda Tandem rPTPpsi (Ptpru) cPTPgamma PTP Domain rPTPgamma (Ptprg) hPTPgamma (PTPRG) PTPgamma ‘Supertype’ 1000 mPTPgamma (Ptprg) xPTPzeta cPTPzeta R5 906 hPTPzeta (PTPRZ1) PTPzeta rPTPzeta (Ptprz1) zPTPalpha (ptpra) xPTPalpha cPTPalpha hPTPalpha (PTPRA) PTPalpha 1000 mPTPalpha (Ptpra) rPTPalpha (Ptpra) R4 hPTPepsilon (PTPRE) 716 mPTPepsilon (Ptpre) rPTPepsilon (Ptpre) PTPepsilon sharkCD45 cCD45 hCD45 (PTPRC) 671 1000 mCD45 (Ptprc) R1/R6 rCD45 (Ptprc) CD45 cypcaCD45 fuCD45 hDEP1 (PTPRJ) rDEP1 (Ptprj) 940 mDEP1 (Ptprj) DEP1 hPTPbeta (PTPRB) 326 mPTPbeta (Ptprb) rPTPbeta PTPbeta hGLEPP1 (PTPRO) 486 rabPTPoc 562 rGLEPP1 (Ptpro) GLEPP1 mPTPphi (Ptpro) R3 989 hPTPS31 (PTPGMC1) rPTPGMC1 (Ptprq) PTPS31/GMC1 hSAP1 (PTPRH) mSAP1 SAP1 rPTPBEM2 mPTPESP (Ptprv) 636 rOSTPTP (Esp) OST-PTP hPCPTP1 (PTPRR) rPCPTP1 (Ptprr) PCPTP 344 997 mPTPSL (Ptprr) hSTEP (PTPN5) 1000 mSTEP (Ptpn5) rSTEP (Ptpn5) STEP R7 hHePTP (PTPN7) mHePTP (Ptpn7) HePTP rLCPTP (Ptpn7) ryPTPN6c zSHP1 hSHP1 (PTPN6) 1000 mSHP1 (Hcph) SHP1 rSHP1 (Ptph6) ryPTPN6b zSHP2 xSHP2 NT2 rSHP2 (Ptpn11) cSHP2 SHP2 hSHP2 (PTPN11) mSHP2 (Ptpn11) hLyPTP (PTPN22) mPEP (Ptpn8) LyPTP mPEST (Ptpn12) 998 hPEST (PTPN12) rRKPTP (Ptpn12) PEST hBDP1 (PTPN18) NT4 mPTPK1 (Ptpn18) rPTP20 BDP1 hPTPD1 (PTPN21) mPTPRL10 (Ptpn21) 1000 rPTP2E (Ptp2E) PTPD1 hPTPD2 (PTPN14) mPTP36 (Ptpn14) NT6 121 723 rPTPD2 PTPD2 zMEG1 hMEG1 (PTPN4) 1000 mMEG1 (Ptpn4) MEG1 hPTPH1 (PTPN3) NT5 mPTPH1 (Ptpn3) PTPH1 zPTP1B (ptp1b) cPTP1B 221 hPTP1B (PTPN1) 1000 mPTP1B (Ptpn1) PTP1B rPTP1B (Ptpn1) zTCPTP NT1 74 514 hTCPTP (PTPN2) mTCPTP (Ptpn2) TCPTP rTCPTP D1 (Ptpn2) hMEG2 (PTPN9) 1000 mMEG2 (Ptpn9) xPTPX10 MEG2 156 xPTPX1 NT3 rPTPTD14 hHDPTP (PTPN23) HDPTP mHDPTP (Ptpn23) NT9 1000 mPTPBL (Ptpn13) 946 hPTPBAS (PTPN13) PTPBAS bPTPBA14 (PTPN13) NT7 1000 hPTPTyp (PTPN20) mPTPTyp (Ptpn20) PTPTyp mIA2 (Ptprn) NT8 hIA2 (PTPRN) rIA2 (Ptprn) PTPIA2 1000 bIA2 (Ptprn) hIA2beta (PTPRN2) macneIA2beta R8 mPTPNP (Ptprn2) PTPIA2beta rPTPNE6 (Ptprn2) http://ptp.cshl.edu or http://science.novonordisk.com/ptp -Page 1- Andersen et al Mol. Cell. Biol. 2001, Andersen et al FASEB J. 2003 Homology Tree of Human PTP Catalytic Domains and Membrane distal PTP domains in RPTPs 0.1 Tandem hPTPalpha D2 (NP_ 002827) PTPRA PTP Domain 1000 ‘Supertype’ hPTPepsilon D2 (NP_ 006495) PTPRE 961 hLAR D2 (NP_ 002831) PTPRF 1000hPTPdelta D2 (NP_ 002830) PTPRD 955 979 hPTPsigma D2 (NP_ 002841) PTPRS hCD45 D2 (NP_ 002829) PTPRC PTP D2 hPTPlamda D2 (NP_ 005695) PTPRU domains 569 1000 hPTPkappa D2 (NP_ 002835) PTPRK 932 hPTPmu D2 (NP_ 002836) PTPRM 818 548 hPTPrho D2 (NP_ 573400) PTPRT hPTPgamma D2 (NP_ 002832) PTPRG 1000 hPTPzeta D2 (NP_ 002842) PTPRZ1 hCD45 D1 (NP_ 002829 PTPRC) 696 hPTPalpha D1 (NP_ 002827) PTPRA 1000 hPTPepsilon D1 (NP_ 006495) PTPRE 203 hPTPlamda D1 (NP_ 005695) PTPRU 1000 hPTPkappa D1 (NP_ 002835) PTPRK 825 804 hPTPmu D1 (NP_ 002836) PTPRM 590 818 hPTPrho D1 (NP_ 573400) PTPRT hPTPsigma D1 (NP_ 002841 PTPRS 1000 hPTPdelta D1 (NP_ 002830) PTPRD 762 607 544 hLAR D1 (NP_ 002831) PTPRF hPTPgamma D1 (NP_ 002832) PTPRG 1000 281 hPTPzeta D1 (NP_ 002842) PTPRZ1 hSAP1 D1 (NP_ 002833) PTPRH 366 hDEP1 D1 (NP_ 002834) PTPRJ 961 988 hPTPbeta D1 (NP_ 002828) PTPRB hGLEPP1 D1 (NP_ 109592) PTPRO 526 hPTPS31 D1 (AR073855) PTPGMC1 hHePTP D1 (NP_ 002823) PTPN7 PTP D1 73 1000 hPCPTP1 D1 (NP_ 002840) PTPRR 994 domains 378 hSTEP D1 (NP_ 116170) PTPN5 hSHP1 D1 (NP_ 002822) PTPN6 1000 hSHP2 D1 (NP_ 002825) PTPN11 hPTPD1 D1 (NP_ 008970) PTPN21 1000 hPTPD2 D1 (NP_ 005392) PTPN14 615 121 hMEG1 D1 (NP_ 002821) PTPN4 1000 284 hPTPH1 D1 (NP_ 002820) PTPN3 hMEG2 D1 (NP_ 002824) PTPN9 445 hPTP1B D1 (NP_ 002818) PTPN1 1000 hTCPTP D1 (NP_ 002819) PTPN2 hPTPBAS D1 (NP_ 006255) PTPN13 952 hPTPTyp D1 (AL050040) PTPN20 hBDP1 D1 (NP_ 055184) PTPN18 1000 hLyPTP D1 (NP_ 057051) PTPN22 1000 hPEST D1 (NP_ 002826) PTPN12 hHDPTP D1 (NP_ 056281) PTPN23 574 hIA2 D1 (NP_ 002837) PTPRN 1000 hIA2beta D1 (NP_ 002838) PTPRN2 http://ptp.cshl.edu or http://science.novonordisk.com/ptp Andersen et al Mol. Cell. Biol. 2001, Andersen et al FASEB J. 2003 Dendogram of Human, Mouse and Rat PTP Domains (Overview of the official PTP gene symbols) 0.1 hPTPsigma (PTPRS) 1000 mPTPsigma (Ptprs) PTPsigma Subtypes rPTPsigma (Ptprd) hPTPdelta (PTPRD) mPTPdelta (Ptprd) PTPdelta R2A hLAR (PTPRF) mLAR (Ptprf) 828 rLAR (Ptprf) LAR hPTPrho (PTPRT) mPTPrho (Ptprt) PTPrho hPTPmu (PTPRM) PTPmu 1000 mPTPmu (Ptprm) 767 hPTPkappa (PTPRK) mPTPkappa (Ptprk) PTPkappa R2B hPTPlamda (PTPRU) mPTPlamda (Ptprl) PTPlambda rPTPpsi (Ptpru) rPTPgamma (Ptprg) 1000 hPTPgamma (PTPRG) PTPgamma 934 mPTPgamma (Ptprg) hPTPzeta (PTPRZ1) R5 rPTPzeta (Ptprz1) PTPzeta mPTPzeta (Ptprz1) hPTPalpha (PTPRA) 1000 mPTPalpha (Ptpra) PTPalpha rPTPalpha (Ptpra) 802 hPTPepsilon (PTPRE) R4 mPTPepsilon (Ptpre) PTPepsilon rPTPepsilon (Ptpre) rCD45 (Ptprc) 614 hCD45 (PTPRC) CD45 mCD45 (Ptprc) R1 hDEP1 (PTPRJ) 934 rDEP1 (Ptprj) DEP1 mDEP1 (Ptprj) hPTPbeta (PTPRB) 550 mPTPbeta (Ptprb) PTPbeta rPTPbeta (Ptprb) hGLEPP1 (PTPRO) rGLEPP1 (Ptpro) GLEPP1 991 mPTPphi (Ptpro) 524 mPTPS31 R3 522 hPTPS31 (PTPRQ) PTPS31 rPTPGMC1 (Ptprq) hSAP1 (PTPRH) mSAP1 SAP1 rPTPBEM2 621 hPTPOST mPTPESP (Ptprv) PTPOST rPTPOST (Esp) hPCPTP1 (PTPRR) 402 rPCPTP1 (Ptprr) PCPTP mPTPSL (Ptprr) 1000 hSTEP (PTPN5) mSTEP (Ptpn5) STEP rSTEP (Ptpn5) R7 hHePTP (PTPN7) mHePTP (Ptpn7) HePTP rLCPTP (Ptpn7) hSHP1 (PTPN6) 1000 mSHP1 (Hcph) SHP1 rSHP1 (Ptph6) rSHP2 (Ptpn11) NT2 hSHP2 (PTPN11) SHP2 mSHP2 (Ptpn11) hLyPTP (PTPN22) mPEP (Ptpn8) LyPTP 998 mPEST (Ptpn12) hPEST (PTPN12) PEST rRKPTP (Ptpn12) NT4 hBDP1 (PTPN18) mPTPK1 (Ptpn18) BDP1 rPTP20 hPTPD1 (PTPN21) 1000 mPTPRL10 (Ptpn21) PTPD1 120 rPTP2E (Ptp2E) hPTPD2 (PTPN14) NT6 740 mPTP36 (Ptpn14) PTPD2 rPTPD2 hMEG1 (PTPN4) 1000 mMEG1 (Ptpn4) MEG1 hPTPH1 (PTPN3) PTPH1 NT5 mPTPH1 (Ptpn3) 245 hPTP1B (PTPN1) 1000 mPTP1B (Ptpn1) PTP1B rPTP1B (Ptpn1) NT1 519 hTCPTP (PTPN2) mTCPTP (Ptpn2) TCPTP rTCPTP (Ptpn2) hMEG2 (PTPN9) MEG2 279 mMEG2 (Ptpn9) NT3 rPTPTD14 hHDPTP (PTPN23) HDPTP mHDPTP (Ptpn23) NT9 1000 hPTPBAS (PTPN13) 941 PTPBAS mPTPBL (Ptpn13) NT7 1000 hPTPTyp (PTPN20) mPTPTyp (Ptpn20) PTPTyp NT8 mIA2 (Ptprn) 1000 hIA2 (PTPRN) PTPIA2 rIA2 (Ptprn) hIA2beta (PTPRN2) R8 mPTPNP (Ptprn2) PTPIA2beta rPTPNE6 (Ptprn2) http://ptp.cshl.edu or http://science.novonordisk.com/ptp Andersen et al (FASEB J) 2003 Homology Tree of Vertebrate PTP Catalytic Domains and Membrane Distal Domains in RPTPs 0.1 979 hPTPsigma D1 NP 002841 PTPRS 978 980 mPTPsigma D1 NP 035348 revise rPTPsigma D1 NP 062013 Ptprd 978 xPTPsigma D1 AAF43607 765 680 cPTPsigma D1 I50212 zPTPsigma D1 CAC44759 1000 1000 xPTPdelta D1 AAF43605 98hP7 TPdelta D1 NP 002830 PTPR mPTPdelta D1 D54689 954 xLAR D1 AAF43606 1000hLAR D1 NP 002831 PTPRF 93m5LAR D1 NP 035343 Ptprf 827 rLAR D1 NP 062122 Ptprf 1000 xPTPrho D1 AAD50295 hP10TP00rho D1 NP 573400 PTPRT 782 mPTPrho D1 NP 067439 Ptprt 1000hPTPmu D1 NP 002836 PTPRM 484 mPTPmu D1 NP 033010 Ptprm 1000 1000 794 hPTPkappa D1 NP 002835 PTPRK mPTPkappa D1 NP 033009 revis 1000 hPTPlamda D1 NP 005695 PTPRU 918 mPTPlamda D1 NP 035344 Ptprl rPTPpsi D1 AAB42210 Fragm 1000 cPTPgamma D1 Q98936 751 rPTPgamma D1 NP 599183 Ptpr 1000 823 hPTPgamma D1 NP 002832 PTPRG mPTPgamma D1 NP 033007 Ptprg 1000 xPTPzeta D1 BAA97445 883 1000 cPTPzeta D1 AAA49015 994 hPTPzeta D1 NP 002842 PTPRZ1 rPTPzeta D1 NP 037212 Ptprz1 1000 zPTPalpha D1 NP 571963 ptpra 994 xPTPalpha D1 AAA17990 831 cPTPalpha D1 AAB04150 1000 97hP0 TPalpha D1 NP 002827 PTPRA m87P2TPalpha D1 AAK56109 Ptpra rPTPalpha D1 NP 036895 Ptpra 1000 hPTPepsilon D1 NP 006495 PTP 766 m10P00TPepsilon D1 NP 035342 Ptp rPTPepsilon D1 XP 215102 Ptp 877 sharkCD45 D1 T43148 998 cCD45 D1 A54080 1000 1000 hCD45 D1 NP 002829 PTPRC 643 525 mCD45 D1 NP 035340 Ptprc rCD45 D1 XP 213985 Ptprc 998 cypcaCD45 D1 BAA92179 fuCD45 D1 CAB96211 1000 hDEP1 D1 NP 002834 PTPRJ 998 948 rDEP1 D1 NP 058965 Ptprj mDEP1 D1 NP 033008 Ptprj 1000 hPTPbeta D1 NP 002828 PTPRB 387 99mP1TPbeta D1 NP 084204 Ptprb rPTPbeta D1 XP 235156 revise 99hGLE4 PP1 D1 NP 109592 PTPRO 450 1000 rabPTPoc D1 AAB16824 341 951rGLEPP1 D1 NP 059032 Ptpro mPTPphi D1 NP 035346 Ptpro 985 1000 hPTPS31 D1 AR073855 PTPGMC1 rPTPGMC1 D1 NP 075214 Ptprq 1000 hSAP1 D1 NP 002833 PTPRH 1000 599 mSAP1 D1 BAC37443 rPTPBEM2 D1 NP 598276 1000 mPTPESP D1 NP 031981 Esp rOSTPTP D1 NP 149090 Esp 1000 hPCPTP1 D1 NP 002840 PTPRR 817 996 rPCPTP1 D1 NP 446046 Ptprr mPTPSL D1 NP 035347 Ptprr 1000 hSTEP D1 NP 116170 PTPN5 1000 99m7STEP D1 NP 038671 Ptpn5 rSTEP D1 NP 062126 Ptpn5 1000 hHePTP D1 NP 002823 PTPN7 10m00HePTP D1 NP 796055 rLCPTP D1 P49445 Ptpn7 821 ryPTPN6c D1 BAA95199 538 zSHP1 D1 AAH44414 1000 hSHP1 D1 NP 002822 PTPN6 1000 999mSHP1 D1 NP 038573 Hcph rSHP1 D1 NP 446360 Ptph6 1000 ryPTPN6b D1 BAA95198 993 zSHP2 D1 AAH45328 900 xSHP2 D1 A55651 302 10rS00HP2 D1 NP 037220 Ptpn11 cS431HP2 D1 JC5167 hS64H6P2 D1 NP 002825 PTPN11 mSHP2 D1 NP 035332 Ptpn11
Load more

Recommended publications
  • SRC Antibody - N-Terminal Region (ARP32476 P050) Data Sheet
    SRC antibody - N-terminal region (ARP32476_P050) Data Sheet Product Number ARP32476_P050 Product Name SRC antibody - N-terminal region (ARP32476_P050) Size 50ug Gene Symbol SRC Alias Symbols ASV; SRC1; c-SRC; p60-Src Nucleotide Accession# NM_005417 Protein Size (# AA) 536 amino acids Molecular Weight 60kDa Product Format Lyophilized powder NCBI Gene Id 6714 Host Rabbit Clonality Polyclonal Official Gene Full Name V-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) Gene Family SH2D This is a rabbit polyclonal antibody against SRC. It was validated on Western Blot by Aviva Systems Biology. At Aviva Systems Biology we manufacture rabbit polyclonal antibodies on a large scale (200-1000 Description products/month) of high throughput manner. Our antibodies are peptide based and protein family oriented. We usually provide antibodies covering each member of a whole protein family of your interest. We also use our best efforts to provide you antibodies recognize various epitopes of a target protein. For availability of antibody needed for your experiment, please inquire (). Peptide Sequence Synthetic peptide located within the following region: QTPSKPASADGHRGPSAAFAPAAAEPKLFGGFNSSDTVTSPQRAGPLAGG This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the Description of Target regulation of embryonic development and cell growth. SRC protein is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the
    [Show full text]
  • PTPN9 Promotes Cell Proliferation and Invasion in Eca109 Cells and Is Negatively Regulated by Microrna-126
    ONCOLOGY LETTERS 14: 1419-1426, 2017 PTPN9 promotes cell proliferation and invasion in Eca109 cells and is negatively regulated by microRNA-126 JUNWEI ZHU1, HAOMIAO LI1, JUN MA2, HAIBO HUANG1, JIANJUN QIN1 and YIN LI1 1Department of Thoracic Surgery, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan 450008; 2Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China Received September 11, 2015; Accepted April 13, 2017 DOI: 10.3892/ol.2017.6315 Abstract. Protein tyrosine phosphatase non-receptor type 9 Using RNA interference, the present study demonstrated that (PTPN9), also named PTP-MEG2, is an important member knockdown of PTPN9 significantly suppressed cell prolifera- of the protein tyrosine phosphatase family that is involved tion and invasion in Eca109. Additionally, it was hypothesized in variety of human diseases. However, the role of PTPN9 that miR-126, described as a tumor suppressor in ESCC, in esophageal squamous cell carcinoma (ESCC) remains to may act at least in part via its inhibition of PTPN9 at the be established. The present evaluated the potential effect and post-transcriptional level. To the best of our knowledge, this is underlying mechanism of action of PTPN9 in ESCC. Immu- the first study to demonstrate that PTPN9 is overexpressed in nohistochemistry was performed to detect PTPN9 protein ESCC and associated with poor survival, and may therefore be expression in 84 ESCC tumor specimens and 30 normal important in the pathogenesis of ESCC. esophageal tissues. The association between positive expres- sion of PTPN9 and clinicopathological features and prognosis Introduction was analyzed. The prognostic role of PTPN9 was further inves- tigated using multivariate regression analysis.
    [Show full text]
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [Show full text]
  • Identification of Chebulinic Acid As a Dual Targeting Inhibitor of Protein
    Bioorganic Chemistry 90 (2019) 103087 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg Short communication Identification of chebulinic acid as a dual targeting inhibitor of protein T tyrosine phosphatases relevant to insulin resistance Sun-Young Yoona,1, Hyo Jin Kangb,1, Dohee Ahna, Ji Young Hwanga, Se Jeong Kwona, ⁎ Sang J. Chunga, a School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea b Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea ARTICLE INFO ABSTRACT Keywords: Natural products as antidiabetic agents have been shown to stimulate insulin signaling via the inhibition of the Protein tyrosine phosphatases (PTPs) protein tyrosine phosphatases relevant to insulin resistance. Previously, we have identified PTPN9 and DUSP9 as Chebulinic acid potential antidiabetic targets and a multi-targeting natural product thereof. In this study, knockdown of PTPN11 Type 2 diabetes increased AMPK phosphorylation in differentiated C2C12 muscle cells by 3.8 fold, indicating that PTPN11 could Glucose-uptake be an antidiabetic target. Screening of a library of 658 natural products against PTPN9, DUSP9, or PTPN11 PTPN9 identified chebulinic acid (CA) as a strong allosteric inhibitor with a slow cooperative binding toPTPN9 PTPN11 (IC50 = 34 nM) and PTPN11 (IC50 = 37 nM), suggesting that it would be a potential antidiabetic candidate. Furthermore, CA stimulated glucose uptake and resulted in increased AMP-activated protein kinase (AMPK) phosphorylation. Taken together, we demonstrated that CA increased glucose uptake as a dual inhibitor of PTPN9 and PTPN11 through activation of the AMPK signaling pathway. These results strongly suggest that CA could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.
    [Show full text]
  • Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3؅-Phosphate Kinase/PTEN Pathway1
    [CANCER RESEARCH 63, 1382–1388, March 15, 2003] Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3؅-Phosphate Kinase/PTEN Pathway1 Ana I. Jimenez, Paloma Fernandez, Orlando Dominguez, Ana Dopazo, and Montserrat Sanchez-Cespedes2 Molecular Pathology Program [A. I. J., P. F., M. S-C.], Genomics Unit [O. D.], and Microarray Analysis Unit [A. D.], Spanish National Cancer Center, 28029 Madrid, Spain ABSTRACT the cell cycle in G1 (8, 9). However, the intrinsic mechanism by which LKB1 activity is regulated in cells and how it leads to the suppression Germ-line mutations in LKB1 gene cause the Peutz-Jeghers syndrome of cell growth is still unknown. It has been proposed that growth (PJS), a genetic disease with increased risk of malignancies. Recently, suppression by LKB1 is mediated through p21 in a p53-dependent LKB1-inactivating mutations have been identified in one-third of sporadic lung adenocarcinomas, indicating that LKB1 gene inactivation is critical in mechanism (7). In addition, it has been observed that LKB1 binds to tumors other than those of the PJS syndrome. However, the in vivo brahma-related gene 1 protein (BRG1) and this interaction is required substrates of LKB1 and its role in cancer development have not been for BRG1-induced growth arrest (10). Similar to what happens in the completely elucidated. Here we show that overexpression of wild-type PJS, Lkb1 heterozygous knockout mice show gastrointestinal hamar- LKB1 protein in A549 lung adenocarcinomas cells leads to cell-growth tomatous polyposis and frequent hepatocellular carcinomas (11, 12). suppression. To examine changes in gene expression profiles subsequent to Interestingly, the hamartomas, but not the malignant tumors, arising in exogenous wild-type LKB1 in A549 cells, we used cDNA microarrays.
    [Show full text]
  • Mir-96-5P Targets PTEN Expression Affecting Radio-Chemosensitivity of HNSCC Cells
    Vahabi et al. Journal of Experimental & Clinical Cancer Research (2019) 38:141 https://doi.org/10.1186/s13046-019-1119-x RESEARCH Open Access miR-96-5p targets PTEN expression affecting radio-chemosensitivity of HNSCC cells Mahrou Vahabi1,2, Claudio Pulito1, Andrea Sacconi1, Sara Donzelli1, Marco D’Andrea3, Valentina Manciocco4, Raul Pellini4, Paola Paci5,6, Giuseppe Sanguineti3, Lidia Strigari7, Giuseppe Spriano8, Paola Muti9, Pier Paolo Pandolfi10, Sabrina Strano1, Shahrokh Safarian2*, Federica Ganci1* and Giovanni Blandino1* Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide. They are typically characterized by a high incidence of local recurrence, which is the most common cause of death in HNSCC patients. TP53 is the most frequently mutated gene in HNSCC and patients carrying TP53 mutations are associated with a higher probability to develop local recurrence. MiRNAs, which are among the mediators of the oncogenic activity of mt-p53 protein, emerge as an appealing tool for screening, diagnosis and prognosis of cancer. We previously identified a signature of 12 miRNAs whose aberrant expression associated with TP53 mutations and was prognostic for HNSCC. Among them miR-96-5p emerges as an oncogenic miRNAs with prognostic significance in HNSCC. Methods: To evaluate the oncogenic role of miR-96-5p in a tumoral context, we performed colony formation, cell migration and cell viability assays in two HNSCC cell lines transfected for miR-96-5p mimic or inhibitor and treated with or without radio/chemo-therapy. In addition, to identify genes positively and negatively correlated to miR-96- 5p expression in HNSCC, we analyzed the correlation between gene expression and miR-96-5p level in the subset of TCGA HNSCC tumors carrying missense TP53 mutations by Spearman and Pearson correlation.
    [Show full text]
  • The Expression Patterns and the Prognostic Roles of PTPN Family Members in Digestive Tract Cancers
    Preprint: Please note that this article has not completed peer review. The expression patterns and the prognostic roles of PTPN family members in digestive tract cancers CURRENT STATUS: UNDER REVIEW Jing Chen The First Affiliated Hospital of China Medical University Xu Zhao Liaoning Vocational College of Medicine Yuan Yuan The First Affiliated Hospital of China Medical University Jing-jing Jing The First Affiliated Hospital of China Medical University [email protected] Author ORCiD: https://orcid.org/0000-0002-9807-8089 DOI: 10.21203/rs.3.rs-19689/v1 SUBJECT AREAS Cancer Biology KEYWORDS PTPN family members, digestive tract cancers, expression, prognosis, clinical features 1 Abstract Background Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members and the prognosis of digestive tract cancers. Method Expression profiling of PTPN family genes in digestive tract cancers were analyzed through ONCOMINE and UALCAN. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMANIA and the protein–protein interaction (PPI) network was built using STRING portal couple with Cytoscape. Data from The Cancer Genome Atlas (TCGA) were downloaded for validation and to explore the relationship of the PTPN expression with clinicopathological parameters and survival of digestive tract cancers. Results Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. For esophageal carcinoma (ESCA), expression of PTPN1, PTPN4 and PTPN12 were upregulated; expression of PTPN20 was associated with poor prognosis.
    [Show full text]
  • 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.
    [Show full text]
  • 1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
    xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A
    [Show full text]
  • Protein Tyrosine Phosphatase PTPN3 Inhibits Lung Cancer Cell Proliferation and Migration by Promoting EGFR Endocytic Degradation
    Oncogene (2015) 34, 3791–3803 © 2015 Macmillan Publishers Limited All rights reserved 0950-9232/15 www.nature.com/onc ORIGINAL ARTICLE Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation M-Y Li1,2, P-L Lai1, Y-T Chou3, A-P Chi1, Y-Z Mi1, K-H Khoo1,2, G-D Chang2, C-W Wu3, T-C Meng1,2 and G-C Chen1,2 Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling. Oncogene (2015) 34, 3791–3803; doi:10.1038/onc.2014.312; published online 29 September 2014 INTRODUCTION sorting EGFR to multivesicular bodies.15 Recently, Ali et al.16 Reversible tyrosine protein phosphorylation by protein tyrosine showed that the ESCRT accessory protein HD-PTP/PTPN23 kinases and protein tyrosine phosphatases (PTPs) acts as a coordinates with the ubiquitin-specific peptidase UBPY to drive molecular switch that regulates a variety of biological pro- EGFR sorting to the multivesicular bodies.
    [Show full text]
  • RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
    RT² Profiler PCR Array (96-Well Format and 384-Well [4 x 96] Format) Human Protein Phosphatases Cat. no. 330231 PAHS-045ZA For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 5700, 7000, 7300, 7500, Format A 7700, 7900HT, ViiA™ 7 (96-well block); Bio-Rad® models iCycler®, iQ™5, MyiQ™, MyiQ2; Bio-Rad/MJ Research Chromo4™; Eppendorf® Mastercycler® ep realplex models 2, 2s, 4, 4s; Stratagene® models Mx3005P®, Mx3000P®; Takara TP-800 RT² Profiler PCR Array, Applied Biosystems models 7500 (Fast block), 7900HT (Fast Format C block), StepOnePlus™, ViiA 7 (Fast block) RT² Profiler PCR Array, Bio-Rad CFX96™; Bio-Rad/MJ Research models DNA Format D Engine Opticon®, DNA Engine Opticon 2; Stratagene Mx4000® RT² Profiler PCR Array, Applied Biosystems models 7900HT (384-well block), ViiA 7 Format E (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (96-well block) Format F RT² Profiler PCR Array, Roche LightCycler 480 (384-well block) Format G RT² Profiler PCR Array, Fluidigm® BioMark™ Format H Sample & Assay Technologies Description The Human Protein Phosphatases RT² Profiler PCR Array profiles the gene expression of the 84 most important and well-studied phosphatases in the mammalian genome. By reversing the phosphorylation of key regulatory proteins mediated by protein kinases, phosphatases serve as a very important complement to kinases and attenuate activated signal transduction pathways. The gene classes on this array include both receptor and non-receptor tyrosine phosphatases, catalytic subunits of the three major protein phosphatase gene families, the dual specificity phosphatases, as well as cell cycle regulatory and other protein phosphatases.
    [Show full text]
  • 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.
    [Show full text]