phosphoprotein phosphatase

Summary

Summary: A group of enzymes removing the serine- or threonine-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16.

Top Publications

  1. pmc Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins
    Sang Youl Park
    Department of Botany and Plant Sciences, University of California at Riverside, Riverside, CA 92521, USA
    Science 324:1068-71. 2009
  2. ncbi Regulators of PP2C phosphatase activity function as abscisic acid sensors
    Yue Ma
    Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D 85354 Freising, Germany
    Science 324:1064-8. 2009
  3. pmc Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling
    V Janssens
    Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Biochem J 353:417-39. 2001
  4. ncbi Serine/threonine phosphatases: mechanism through structure
    Yigong Shi
    Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
    Cell 139:468-84. 2009
  5. pmc Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha
    I Novoa
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 153:1011-22. 2001
  6. ncbi Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase
    Andrew P Somlyo
    Dept of Molecular Physiology and Biological Physics, Univ of Virginia, PO Box 800736, Charlottesville, VA 22908 0736
    Physiol Rev 83:1325-58. 2003
  7. pmc Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase
    Dan Liu
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 188:809-20. 2010
  8. pmc Structural mechanism of abscisic acid binding and signaling by dimeric PYR1
    Noriyuki Nishimura
    Division of Biological Sciences, Cell and Developmental Biology Section, University of California at San Diego, La Jolla, CA 92093, USA
    Science 326:1373-9. 2009
  9. ncbi From promiscuity to precision: protein phosphatases get a makeover
    David M Virshup
    Program in Cancer and Stem Cell Biology, Duke NUS Graduate Medical School Singapore, Singapore, Republic of Singapore
    Mol Cell 33:537-45. 2009
  10. ncbi Molecular aspects of seed dormancy
    Ruth Finkelstein
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106 9610, USA
    Annu Rev Plant Biol 59:387-415. 2008

Detail Information

Publications363 found, 100 shown here

  1. pmc Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins
    Sang Youl Park
    Department of Botany and Plant Sciences, University of California at Riverside, Riverside, CA 92521, USA
    Science 324:1068-71. 2009
    ..Our results illustrate the power of the chemical genetic approach for sidestepping genetic redundancy...
  2. ncbi Regulators of PP2C phosphatase activity function as abscisic acid sensors
    Yue Ma
    Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D 85354 Freising, Germany
    Science 324:1064-8. 2009
    ..Other RCARs also mediated ABA-dependent regulation of ABI1 and ABI2, consistent with a combinatorial assembly of receptor complexes...
  3. pmc Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling
    V Janssens
    Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Biochem J 353:417-39. 2001
    ..Finally, the de-regulation of PP2A in some specific pathologies will be touched upon...
  4. ncbi Serine/threonine phosphatases: mechanism through structure
    Yigong Shi
    Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
    Cell 139:468-84. 2009
    ..Here, we discuss biochemical and structural investigations that advance the mechanistic understanding of the three major classes of PSPs, with a focus on PP2A...
  5. pmc Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha
    I Novoa
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 153:1011-22. 2001
    ....
  6. ncbi Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase
    Andrew P Somlyo
    Dept of Molecular Physiology and Biological Physics, Univ of Virginia, PO Box 800736, Charlottesville, VA 22908 0736
    Physiol Rev 83:1325-58. 2003
    ..It is a potentially important therapeutic target and a subject for translational research...
  7. pmc Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase
    Dan Liu
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 188:809-20. 2010
    ..In total, our results support a positive feedback mechanism by which Aurora B activity at kinetochores not only targets substrates directly, but also prevents localization of the opposing phosphatase...
  8. pmc Structural mechanism of abscisic acid binding and signaling by dimeric PYR1
    Noriyuki Nishimura
    Division of Biological Sciences, Cell and Developmental Biology Section, University of California at San Diego, La Jolla, CA 92093, USA
    Science 326:1373-9. 2009
    ..Site-directed PYR1 mutants designed to disrupt hormone binding lose ABA-triggered interactions with type 2C protein phosphatase partners in planta...
  9. ncbi From promiscuity to precision: protein phosphatases get a makeover
    David M Virshup
    Program in Cancer and Stem Cell Biology, Duke NUS Graduate Medical School Singapore, Singapore, Republic of Singapore
    Mol Cell 33:537-45. 2009
    ..As recent publications illustrate, these regulatory subunits confer specificity, selectivity, localization, and regulation on these important enzymes...
  10. ncbi Molecular aspects of seed dormancy
    Ruth Finkelstein
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106 9610, USA
    Annu Rev Plant Biol 59:387-415. 2008
    ..The net result is a slightly heterogeneous response, thereby providing more temporal options for successful germination...
  11. ncbi Protein phosphatase 1--targeted in many directions
    Patricia T W Cohen
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD15EH, Scotland, UK
    J Cell Sci 115:241-56. 2002
    ..Understanding of the mode of action of PP1c complexes may facilitate development of drugs that target particular PP1c complexes and thereby modulate the phosphorylation state of a very limited subset of proteins...
  12. ncbi The physiological relevance of protein phosphatase 1 and its interacting proteins to health and disease
    M Fardilha
    Centre for Cell Biology, University of Aveiro, Aveiro, Portugal
    Curr Med Chem 17:3996-4017. 2010
    ..Further, it compiles 129 PP1-PIP relevant physiological interactions that are well documented in the literature. Finally, the use of PIPs as therapeutic targets will be addressed...
  13. pmc Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damage
    Eric Batchelor
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 30:277-89. 2008
    ....
  14. ncbi Shugoshin collaborates with protein phosphatase 2A to protect cohesin
    Tomoya S Kitajima
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
    Nature 441:46-52. 2006
    ..Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis...
  15. ncbi Wip1 phosphatase modulates ATM-dependent signaling pathways
    Sathyavageeswaran Shreeram
    Institute of Molecular and Cell Biology, 61 Bioplis Drive, Proteos, 138673, Singapore
    Mol Cell 23:757-64. 2006
    ..We propose that the Wip1 phosphatase is an integral component of an ATM-dependent signaling pathway...
  16. ncbi A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery
    Michael Christopher Keogh
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 439:497-501. 2006
    ..The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint...
  17. ncbi Docking motif-guided mapping of the interactome of protein phosphatase-1
    Annick Hendrickx
    Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Chem Biol 16:365-71. 2009
    ..Notably, an interaction network linking PP1 interactors discloses a pleiotropic role of PP1 in cell polarity...
  18. pmc The extended PP1 toolkit: designed to create specificity
    Mathieu Bollen
    Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B 3000 Leuven, Belgium
    Trends Biochem Sci 35:450-8. 2010
    ..These novel insights offer perspectives for the therapeutic targeting of PP1 by interfering with the binding of PIPs or substrates...
  19. ncbi Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
    Yongna Xing
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544, USA
    Cell 127:341-53. 2006
    ..These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology...
  20. ncbi Protein phosphatases 2A and 1 interact with occludin and negatively regulate the assembly of tight junctions in the CACO-2 cell monolayer
    Ankur Seth
    Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Biol Chem 282:11487-98. 2007
    ..This study shows that PP2A and PP1 directly interact with occludin and negatively regulate the assembly of TJ by modulating the phosphorylation status of occludin...
  21. pmc Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis
    Markus Posch
    Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 191:61-74. 2010
    ..Sds22 regulates PP1 targeting to the kinetochore, accumulation of phospho-aurora B, and force generation at the kinetochore-microtubule interface...
  22. pmc Arabidopsis C-terminal domain phosphatase-like 1 and 2 are essential Ser-5-specific C-terminal domain phosphatases
    Hisashi Koiwa
    Department of Horticultural Sciences, Texas A and M University, College Station, TX 77843 2133, USA
    Proc Natl Acad Sci U S A 101:14539-44. 2004
    ..These results indicate that CPL1 and CPL2 exemplify a unique family of CTD Ser-5-specific phosphatases with an essential role in plant growth and development...
  23. pmc Quantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunit
    Bungo Akiyoshi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genes Dev 23:2887-99. 2009
    ..These data suggest that Fin1 is a PP1 regulatory subunit whose spatial and temporal activity must be precisely controlled to ensure genomic stability...
  24. pmc Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis
    Taishi Umezawa
    Gene Discovery Research Team, RIKEN Plant Science Center, 3 1 1 Kouyadai, Tsukuba, Ibaraki 305 0074, Japan
    Proc Natl Acad Sci U S A 106:17588-93. 2009
    ..Our results demonstrate that group A PP2Cs act as 'gatekeepers' of subclass III SnRK2s, unraveling an important regulatory mechanism of ABA signaling...
  25. ncbi Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity
    Dmitry V Bulavin
    Gene Response Section, Bethesda, Maryland 20892, USA
    Nat Genet 31:210-5. 2002
    ..These findings suggest that inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification contributes to the development of human cancers by suppressing p53 activation...
  26. ncbi Emerging roles of nuclear protein phosphatases
    Greg B G Moorhead
    Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary Alberta, Canada T2N 1N4
    Nat Rev Mol Cell Biol 8:234-44. 2007
    ....
  27. ncbi Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility
    Margarida Fardilha
    Signal Transduction Laboratory, Centre for Cell Biology, Health Sciences Department and Biology Department, University of Aveiro, Campus de Santiago, 3810 193 Aveiro, Portugal
    Mol Hum Reprod 17:466-77. 2011
    ..Furthermore, the potential relevance of targeting PP1-PIPs complexes to infertility diagnostics and therapeutics as well as to male contraception is also discussed...
  28. pmc Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability
    Laura Trinkle-Mulcahy
    University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 172:679-92. 2006
    ..The data indicate that Repo-Man forms an essential complex with PP1gamma and is required for the recruitment of PP1 to chromatin...
  29. ncbi Identification of the human testis protein phosphatase 1 interactome
    Margarida Fardilha
    Signal Transduction Laboratory, Centre for Cell Biology, Biology Department, University of Aveiro, 3810 193 Aveiro, Portugal
    Biochem Pharmacol 82:1403-15. 2011
    ..In fact, such diversity in PP1 regulators makes them excellent targets for pharmacological intervention...
  30. ncbi Structure of the protein phosphatase 2A holoenzyme
    Yanhui Xu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 127:1239-51. 2006
    ..This structure reveals significant ramifications for understanding the function and regulation of PP2A...
  31. ncbi PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation
    Zhanyun Tang
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA
    Dev Cell 10:575-85. 2006
    ..Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1...
  32. pmc PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints
    Xiongbin Lu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 19:1162-74. 2005
    ..These homeostatic functions may be partially responsible for the oncogenic effects of PPM1D when it is amplified and overexpressed in human tumors...
  33. ncbi Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin
    Ryusuke Niwa
    Department of Molecular Genetics, The Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Cell 108:233-46. 2002
    ..Furthermore, SSH and the hSSHs dephosphorylated P cofilin in cultured cells and in cell-free assays. Our results strongly suggest that the SSH family plays a pivotal role in actin dynamics by reactivating ADF/cofilin in vivo...
  34. ncbi Three SnRK2 protein kinases are the main positive regulators of abscisic acid signaling in response to water stress in Arabidopsis
    Yasunari Fujita
    Biological Resources Division, Japan International Research Center for Agricultural Sciences, Tsukuba, Ibaraki, 305 8686, Japan
    Plant Cell Physiol 50:2123-32. 2009
    ..Together, our results indicate that SRK2D/E/I function as main positive regulators, and suggest that ABA signaling is controlled by the dual modulation of SRK2D/E/I and group-A PP2Cs...
  35. ncbi Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway
    Dmitry V Bulavin
    Gene Response Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 36:343-50. 2004
    ..We conclude that inactivation or depletion of the Wip1 phosphatase with resultant p38 MAPK activation suppresses tumor appearance by modulating the Cdkn2a tumor-suppressor locus...
  36. pmc Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner
    M Fiscella
    Advanced BioScience Laboratories Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 94:6048-53. 1997
    ..Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation. These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner...
  37. ncbi Regulation of protein kinase cascades by protein phosphatase 2A
    T A Millward
    Friedrich Miescher Institut, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
    Trends Biochem Sci 24:186-91. 1999
    ..There is increasing evidence that PP2A activity is regulated by extracellular signals and during the cell cycle. Thus, PP2A is likely to play an important role in determining the activation kinetics of protein kinase cascades...
  38. ncbi PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms
    John Brognard
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA
    Mol Cell 25:917-31. 2007
    ..Our data unveil a mechanism to selectively terminate Akt-signaling pathways through the differential inactivation of specific Akt isoforms by specific PHLPP isoforms...
  39. ncbi PTG, a protein phosphatase 1-binding protein with a role in glycogen metabolism
    J A Printen
    Department of Physiology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Science 275:1475-8. 1997
    ..These results suggest that PTG is critical for glycogen metabolism, possibly functioning as a molecular scaffold...
  40. pmc Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2
    Matthew H Brush
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 23:1292-303. 2003
    ..These data provide new insights into the mode of action of GADD34 in assembling an ER-associated eIF-2 alpha phosphatase that regulates protein translation in mammalian cells...
  41. ncbi Regulation of cell migration by the C2 domain of the tumor suppressor PTEN
    Myrto Raftopoulou
    Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, University College London, Gower Street, London WC1E 6BT, UK
    Science 303:1179-81. 2004
    ..The ability of PTEN to control cell migration through its C2 domain is likely to be an important feature of its tumor suppressor activity...
  42. pmc KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint
    Jessica S Rosenberg
    Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA
    Curr Biol 21:942-7. 2011
    ..We propose that the PP1-Spc105 interaction enables local regulation of dynamic phosphorylation and dephosphorylation at the kinetochore to couple microtubule attachment and SAC silencing...
  43. pmc Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E
    Yumi Kim
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 142:444-55. 2010
    ....
  44. ncbi A two-component system that regulates an osmosensing MAP kinase cascade in yeast
    T Maeda
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, Massachusetts
    Nature 369:242-5. 1994
    ..Here we describe a two-component system in Saccharomyces cerevisiae that regulates an osmosensing MAP kinase cascade...
  45. pmc Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)
    Carolyn A Worby
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093 0721, USA
    J Biol Chem 283:4069-76. 2008
    ..These results suggest an additional mechanism, involving laforin and malin, in regulating glycogen metabolism...
  46. ncbi Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress
    Yanjun Ma
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 278:34864-73. 2003
    ....
  47. pmc Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt
    Xin Li
    Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA
    EMBO Rep 12:818-24. 2011
    ..Thus, our findings identify a functional interaction between PHLPP1 and Scrib in negatively regulating Akt signalling...
  48. ncbi Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis
    Pavel Tsaytler
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Science 332:91-4. 2011
    ..This favored protein folding and thereby rescued cells from protein misfolding stress. Thus, regulatory subunits of phosphatases are drug targets, a property used here to restore proteostasis in stressed cells...
  49. pmc Characterisation and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its essential role using RNA interference
    Rajinder Kumar
    Department of Biochemistry and Molecular Biology MSB 2370, University of South Alabama, College of Medicine, 307 University Blvd, Mobile, AL 36688 0002, USA
    Malar J 1:5. 2002
    ..Previous evidence suggested a PP1-like activity in Plasmodium falciparum, not yet identified at the molecular level...
  50. pmc A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication
    Dipanjan Chowdhury
    Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 31:33-46. 2008
    ..Therefore, gamma-H2AX elimination at DNA damage foci is required for DNA damage repair, but accomplishing this task involves distinct phosphatases with potentially overlapping roles...
  51. ncbi Structure and mechanism of the phosphotyrosyl phosphatase activator
    Yang Chao
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Mol Cell 23:535-46. 2006
    ..This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function...
  52. ncbi Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution
    Hugo Ceulemans
    Afdeling Biochemie, Katholieke Universiteit Leuven, Belgium
    Bioessays 24:371-81. 2002
    ..Unexpectedly, our analysis has also enabled us to classify nine poorly characterized proteins as likely regulators of PP1...
  53. pmc PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4
    Ginny I Chen
    Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario M4M 2Y8, Canada
    J Biol Chem 283:29273-84. 2008
    ..PP4R3, and alpha4, and that the regulatory subunits of PP4c have evolved different modes of interaction with the catalytic subunit...
  54. ncbi Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase
    H Fujimoto
    1Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7 5 1, Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Cell Death Differ 13:1170-80. 2006
    ....
  55. ncbi The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation
    A Y Ali
    Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
    Oncogene 31:2175-86. 2012
    ..These findings extend the current knowledge on the molecular and cellular basis of cisplatin resistance and offer the rationale for PPMID as a potential target for treatment of chemoresistant OVCA...
  56. ncbi Small CTD phosphatases function in silencing neuronal gene expression
    Michele Yeo
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 307:596-600. 2005
    ..Likewise, small interfering RNA directed to the single Drosophila SCP unmasks neuronal gene expression in S2 cells. Thus, SCP activity is an evolutionarily conserved transcriptional regulator that acts globally to silence neuronal genes...
  57. pmc Protein phosphatase-1 activates CDK9 by dephosphorylating Ser175
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America
    PLoS ONE 6:e18985. 2011
    ..Collectively, our results point to CDK9 Ser175 as novel PP1-regulatory site which dephosphorylation upregulates CDK9 activity and contribute to the activation of HIV-1 transcription...
  58. pmc Ypi1, a positive regulator of nuclear protein phosphatase type 1 activity in Saccharomyces cerevisiae
    Jennifer P Bharucha
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
    Mol Biol Cell 19:1032-45. 2008
    ..These results, together with genetic interactions among YPI1, GLC7, and SDS22 mutants, indicate that Ypi1 and Sds22 are positive regulators of the nuclear Glc7 activity that is required for mitosis...
  59. pmc PYR/PYL/RCAR family members are major in-vivo ABI1 protein phosphatase 2C-interacting proteins in Arabidopsis
    Noriyuki Nishimura
    Division of Biological Sciences, Cell and Developmental Biology Section and Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0116, USA
    Plant J 61:290-9. 2010
    ....
  60. ncbi Mammalian GADD34, an apoptosis- and DNA damage-inducible gene
    M C Hollander
    Laboratory of Molecular Pharmacology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 272:13731-7. 1997
    ..The association of GADD34 expression with certain types of apoptosis and its homology with a known apoptosis regulator suggests that GADD34 may play a role in apoptosis as well...
  61. ncbi Combinatorial control of protein phosphatase-1
    M Bollen
    Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, B 3000, Leuven, Belgium
    Trends Biochem Sci 26:426-31. 2001
    ..Hormones, growth factors and metabolites control the function of PP1 holoenzymes mainly by modulating the interaction of the subunits...
  62. pmc PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling
    Ruichuan Chen
    Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China
    Genes Dev 22:1356-68. 2008
    ..Thus, through cooperatively dephosphorylating Cdk9 in response to Ca2+ signaling, PP2B and PP1alpha alter the P-TEFb functional equilibrium through releasing P-TEFb from 7SK snRNP for transcription...
  63. ncbi Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3
    Fang Zhang
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Biol Chem 278:33067-77. 2003
    ..Finally, evidence is presented that N-terminal phosphorylation of GSK-3 can be regulated by the GSK-3-dependent protein phosphatase-1.inhibitor-2 complex...
  64. pmc The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways
    Xiongbin Lu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
    Cancer Metastasis Rev 27:123-35. 2008
    ..We present evidence that the suppression of p53, p38 MAP kinase, and ATM/ATR signaling pathways by Wip1 are important components of its oncogenicity when it is amplified and overexpressed in human cancers...
  65. pmc Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases
    Fen Fen Soon
    Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA
    Science 335:85-8. 2012
    ..These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites...
  66. ncbi WIP1 phosphatase at the crossroads of cancer and aging
    Xavier Le Guezennec
    Institute of Molecular and Cell Biology, Cell Cycle Control and Tumorigenesis Group, 61 Biopolis Drive, Proteos, Singapore
    Trends Biochem Sci 35:109-14. 2010
    ..These emerging functions of WIP1 make it a potent therapeutic target against cancer and aging...
  67. pmc Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors
    John C Meadows
    Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK
    Dev Cell 20:739-50. 2011
    ..These data demonstrate that at least two distinct pools of PP1, one kinetochore associated and the other motor associated, are needed to silence the spindle checkpoint...
  68. ncbi Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-beta pathways
    Gopal Sapkota
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 281:40412-9. 2006
    ....
  69. ncbi Organization and function of APT, a subcomplex of the yeast cleavage and polyadenylation factor involved in the formation of mRNA and small nucleolar RNA 3'-ends
    Eduard Nedea
    Banting and Best Department of Medical Research and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 278:33000-10. 2003
    ..Ref2 and Pta1 similarly affect at least one snoRNA transcript...
  70. pmc A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination
    Dong Hyun Lee
    1 Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA 2 Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 17:365-72. 2010
    ..These observations provide new insight into the role and regulation of RPA phosphorylation in HR-mediated repair...
  71. pmc Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution
    A K Das
    Laboratory of Molecular Biophysics, University of Oxford, UK
    EMBO J 15:6798-809. 1996
    ....
  72. ncbi Nuclear localization of the mutant protein phosphatase abi1 is required for insensitivity towards ABA responses in Arabidopsis
    Danièle Moes
    Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D 85354 Freising, Germany
    Plant J 54:806-19. 2008
    ..Thus, abi1-1 acts as a hypermorphic allele, and ABI1 reprograms sensitivity towards ABA in the nucleus...
  73. ncbi MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo
    H Sun
    Cold Spring Harbor Laboratory, New York 11724 2208
    Cell 75:487-93. 1993
    ..The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK. These findings suggest that 3CH134 is a physiological MAP kinase phosphatase; we propose the name MKP-1 for this phosphatase...
  74. ncbi The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity
    Andreas Hochwagen
    Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, E17 233, 40 Ames Street, Cambridge, Massachusetts 02139, USA
    Cell 122:861-73. 2005
    ..Our findings define a branch of the recombination checkpoint involved in the adaptation to persistent chromosomal damage and a critical function for FK506 binding proteins during meiosis...
  75. ncbi The Glc7 phosphatase subunit of the cleavage and polyadenylation factor is essential for transcription termination on snoRNA genes
    Eduard Nedea
    Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada
    Mol Cell 29:577-87. 2008
    ..Swd2 is also a subunit of the Set1c histone H3K4 methyltransferase complex and is required for its stability and optimal methyltransferase activity...
  76. pmc Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A
    Aaron A Goodarzi
    Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
    EMBO J 23:4451-61. 2004
    ..We propose that PP2A plays an important role in the regulation of ATM autophosphorylation and activity in vivo...
  77. pmc Stress-induced gene expression requires programmed recovery from translational repression
    Isabel Novoa
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    EMBO J 22:1180-7. 2003
    ....
  78. ncbi PPM1D is a potential therapeutic target in ovarian clear cell carcinomas
    David S P Tan
    Department of Histopathology and Gynecologic Oncology, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom
    Clin Cancer Res 15:2269-80. 2009
    ..To identify therapeutic targets in ovarian clear cell carcinomas, a chemoresistant and aggressive type of ovarian cancer...
  79. pmc PHLiPPing the switch on Akt and protein kinase C signaling
    John Brognard
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0721, USA
    Trends Endocrinol Metab 19:223-30. 2008
    ..This review focuses on the function of PHLPP1 and PHLPP2 in modulating signaling by Akt and PKC...
  80. pmc Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D
    Robert C Castellino
    Department of Pediatrics, Texas Children s Cancer Center, Baylor College of Medicine, 6621 Fannin Street, MC 3 3320, Houston, TX 77030, USA
    J Neurooncol 86:245-56. 2008
    ..These results indicate that medulloblastoma express significant levels of WIP1 that modulate genotoxic responsiveness by negatively regulating p53...
  81. pmc Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase
    Sathyavageeswaran Shreeram
    Institute of Molecular and Cell Biology, Singapore, 138673
    J Exp Med 203:2793-9. 2006
    ..We propose that Wip1 phosphatase is critical for regulating the ATM-mediated tumor surveillance network...
  82. pmc Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites
    Michael J Ragusa
    Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, USA
    Nat Struct Mol Biol 17:459-64. 2010
    ..Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity...
  83. ncbi Protein phosphatase 1 is a molecular constraint on learning and memory
    David Genoux
    Institute of Cell Biology, Swiss Federal Institute of Technology, Department of Biology, ETH Honggerberg, CH 8093 Zurich, Switzerland
    Nature 418:970-5. 2002
    ..Our findings emphasize the physiological importance of PP1 as a suppressor of learning and memory, and as a potential mediator of cognitive decline during ageing...
  84. pmc Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase
    Kelly Tatchell
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
    Proc Natl Acad Sci U S A 108:3994-9. 2011
    ..Together, our results suggest that TORC1 positively regulates the Glc7 activity that opposes Ipl1 and provide a mechanism to tie nutritional status with mitotic regulation...
  85. ncbi The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis
    Mei Kong
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 306:695-8. 2004
    ..Thus, mammalian cell viability depends on repression of transcription-initiated apoptosis mediated by a component of PP2A...
  86. pmc Microarray expression analyses of Arabidopsis guard cells and isolation of a recessive abscisic acid hypersensitive protein phosphatase 2C mutant
    Nathalie Leonhardt
    Cell and Developmental Biology Section, Division of Biological Sciences, and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093 0116, USA
    Plant Cell 16:596-615. 2004
    ..A T-DNA disruption mutation in AtP2C-HA confers ABA-hypersensitive regulation of stomatal closing and seed germination. The presented data provide a basis for cell type-specific genomic scale analyses of gene function...
  87. ncbi Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast
    Ethel Queralt
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Cell 125:719-32. 2006
    ..These findings allow us to present a new quantitative model for mitotic exit in budding yeast...
  88. pmc PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance
    Sean M Crosson
    Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0650, USA
    J Clin Invest 111:1423-32. 2003
    ..These data suggest that PTG plays a critical role in glycogen synthesis and is necessary to maintain the appropriate metabolic balance for the partitioning of fuel substrates between glycogen and lipid...
  89. pmc AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting subunit of the R5/PTG-protein phosphatase 1 holoenzyme, and accelerates its down-regulation by the laforin-malin complex
    Santiago Vernia
    Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas CSIC and CIBER de Enfermedades Raras CIBERER, Jaime Roig 11, Valencia 46010, Spain
    J Biol Chem 284:8247-55. 2009
    ..Thus, our results define a novel role of AMPK in glycogen homeostasis...
  90. ncbi The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Cell 8:355-68. 2005
    ..Thus, functional inactivation of PP2A is essential for BCR/ABL leukemogenesis and, perhaps, required for blastic transformation...
  91. ncbi Modulation of drought resistance by the abscisic acid receptor PYL5 through inhibition of clade A PP2Cs
    Julia Santiago
    Instituto de Biologia Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas UPV, ES 46022 Valencia, Spain
    Plant J 60:575-88. 2009
    ..Moreover, we show that enhanced resistance to drought can be obtained through PYL5-mediated inhibition of clade A PP2Cs...
  92. ncbi Evolution of protein phosphatases in plants and animals
    Greg B G Moorhead
    Department of Biological Sciences, University of Calgary, 2500 University Drive N W, Calgary, Alberta, Canada
    Biochem J 417:401-9. 2009
    ..In the present review, we discuss the evolution of the PTPs, the serine/threonine specific PPP (phosphoprotein phosphatase) and PPM (metallo-dependent protein phosphatase) families and the more recently discovered phosphatases ..
  93. ncbi A protein phosphatase 2C involved in ABA signal transduction in Arabidopsis thaliana
    K Meyer
    Institute of Plant Sciences, Swiss Federal Institute of Technology, Zurich
    Science 264:1452-5. 1994
    ..Thus, the control of the phosphorylation state of cell signaling components by the ABI1 product could mediate pleiotropic hormone responses...
  94. ncbi Germline mutations in PTEN are present in Bannayan-Zonana syndrome
    D J Marsh
    Nat Genet 16:333-4. 1997
  95. pmc A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo
    Thomas Fellner
    Institute of Medical Biochemistry, Division of Molecular Biology, Vienna Biocenter, University of Vienna, A 1030 Vienna, Austria
    Genes Dev 17:2138-50. 2003
    ..Complementation and RNA-interference experiments showed that PTPA fulfills an essential function conserved from yeast to man...
  96. pmc Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system
    A M Zhabotinsky
    Department of Chemistry and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    Biophys J 79:2211-21. 2000
    ..They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons...
  97. pmc PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci phosphorylation
    Hongge Jia
    Sealy Center for Cancer Cell Biology, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Development 136:307-16. 2009
    ..Taken together, our results suggest that PP4 and PP2A are two phosphatases that act at different positions of the Hh signaling cascade...
  98. ncbi Protein phosphatase 2A: a panoply of enzymes
    D M Virshup
    Departments of Pediatrics and Oncological Sciences, 5C334 School of Medicine, University of Utah, Salt Lake City, 84132, USA david
    Curr Opin Cell Biol 12:180-5. 2000
    ..During the past year, studies have shown that protein phosphatase 2A influences events ranging from the initiation of DNA replication to vertebrate axis formation to apoptosis...
  99. pmc Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast
    Benjamin A Pinsky
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109, USA
    Curr Biol 19:1182-7. 2009
    ..We therefore propose that PP1 activity silences the checkpoint by reversing key phosphorylation events...
  100. ncbi The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A
    M Li
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, Hershey 17033, USA
    J Biol Chem 271:11059-62. 1996
    ..The results indicate that SET is a potent and specific inhibitor of PP2A and suggest that impaired regulation of PP2A may contribute to acute myeloid leukemogenesis...
  101. pmc PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation
    Judy Qiju Wu
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Nat Cell Biol 11:644-51. 2009
    ..Thus, Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated dephosphorylation...

Research Grants68

  1. Gene Therapy with Cardiotropic Vectors for the Treatment of Heart Failure
    Roger J Hajjar; Fiscal Year: 2013
    ....
  2. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2013
    ..Importantly, our findings will have important implications for other diseases where TNF signaling and inflammation play a central role. ..
  3. Combined neuroprotection and metabolic correction to treat leukodystrophies
    ERNESTO ROQUE BONGARZONE; Fiscal Year: 2013
    ....
  4. Protein Phosphatase Regulation of the Principal Renal Sodium Transporter NHE3
    Ion Alexandru Bobulescu; Fiscal Year: 2013
    ....
  5. FACTORS THAT MODIFY INSULIN ACTION
    Maria G Buse; Fiscal Year: 2012
    ..by mTOR will be addressed, including dysregulation of actin dynamics and possible activation of a phosphoprotein phosphatase(s)...
  6. Mitogen-activated Protein Kinases and NF-kB Activation in Vascular Smooth Muscle
    Bingbing Jiang; Fiscal Year: 2010
    ....
  7. High Throughput Screen for Novel Anti-Rheumatic Compounds
    Dale J Christensen; Fiscal Year: 2010
    ..In this we propose to develop assays that will help to identify these novel drug leads that can be used to develop a new anti-RA therapy. ..
  8. Reversible phosphorylation in Hedgehog signaling
    ALAN ZHU; Fiscal Year: 2013
    ..abstract_text> ..
  9. Mechanisms of respiratory long-term facilitation
    Gordon S Mitchell; Fiscal Year: 2013
    ....
  10. Interferon Alpha: The Link Between Lupus and Endothelial Dysfunction
    JOY N BUIE; Fiscal Year: 2013
    ..Finally, the student will submit work for publication in peer-reviewed journals. ..
  11. Cardiac Sarcoplasmic Reticulum Calcium Cycling Proteins
    Evangelia G Kranias; Fiscal Year: 2013
    ..Our studies will clearly advance our knowledge on these two protein players involved in cardiac function and dysfunction, which may lead to better therapeutic avenues in heart failure. ..
  12. Investigational Safety and Toxicity Studies of Subcutaneous COG1410 for Alzheimer
    MICHAEL PETER VITEK; Fiscal Year: 2013
    ..With clinical studies showing that subcutaneous COG1410 can be safely given to human subjects, we will have achieved a significant milestone that reduces the risks and enables substantive commercialization activities to proceed. ..
  13. Regulation of Drosophila arrestins in light adaptation
    Bih Hwa Shieh; Fiscal Year: 2012
    ..We propose that CaMKII, by promoting phosphorylation of visual arrestins, is critical for the negative regulation of the visual response. Moreover, the activity of CaMKII may be tightly modulated by PP2A. ..
  14. The role of MID1/MID2 in regulating epithelial adhesion
    CATHERINE KOTO; Fiscal Year: 2013
    ....
  15. Lipid electrophile adduction of Pin1 and effects on substrate binding &activity
    Christopher D Aluise; Fiscal Year: 2013
    ..The proposed research allows for significant insight into the cellular response to Pin1 protein modification as a consequence of lipid peroxidation. ..
  16. Ethanol-mediated cilia motility dysfunction
    Joseph H Sisson; Fiscal Year: 2013
    ..The studies we propose will greatly extend our knowledge of how to prevent and treat AICD and will expand our insight into how alcohol alters cilia molecules critical for airway cilia function. 1 ..
  17. The role of Twist family bHLH factors in limb morphogenesis
    Anthony B Firulli; Fiscal Year: 2013
    ..The goal of this proposal is to further define the genetic and molecular mechanisms that control Twist-family behavior and regulate both established and novel limb transcriptional programs. ..
  18. Protein Phosphatase Inhibitor-1 and vascular smooth muscle cell function
    Lahouaria Hadri; Fiscal Year: 2013
    ..Defining the mechanisms of I-1 and its physiological consequences, will be of great relevance in the analysis and future proposal of therapies to prevent and perhaps reverse neointima formation after angioplasty. ..
  19. Regulation of Circadian Transcription
    Paul E Hardin; Fiscal Year: 2013
    ..This work will reveal novel features of the circadian timekeeping mechanism in Drosophila that are likely to be conserved in all animals including humans. ..
  20. Cellular Targets of Polyomavirus Tumor Antigens
    David C Pallas; Fiscal Year: 2012
    ..Drugs that function at the level of this new target would likely be less toxic, and therefore more useful for anti-cancer therapy. ..
  21. Mechanisms Regulating Reversal of Malignancy
    Priscilla Furth; Fiscal Year: 2009
    ..2. c. Test if pharmacological RXRalpha and/or PPARgamma agonists alone or in combination prevent development of ERalpha ductal hyperplasia and DCIS. ..
  22. Protection of Centromeric Cohesion by Bub1 and Sgo1
    Hongtao Yu; Fiscal Year: 2010
    ....
  23. PRODUCTS OF THE TRANSFORMING GENES OF POLYOMAVIRUS
    Brian S Schaffhausen; Fiscal Year: 2013
    ..Using these viruses, we seek to identify new pathways responsible for tumor growth, invasion and metastasis. We expect this will improve our understanding of cancer and offer new possibilities for its treatment. ..
  24. ROLE OF PTG IN ADIPOCYTIC GLYCOGEN METABOLISM
    Matthew J Brady; Fiscal Year: 2012
    ..We will also determine the impact of altering glycogen storage in fat cells on their function in vitro and in vivo. ..
  25. Protein Phosphatase Action in Mammalian Spermatogenesis and Sperm Function
    Srinivasan Vijayaraghavan; Fiscal Year: 2012
    ..We will identify how PP1? gene and its protein product PP1?2 in testis and spermatozoa are responsible for sperm formation and function. ..
  26. Regulation of Centrosome Assembly by Phosphorylation
    Mi Hye Song; Fiscal Year: 2012
    ..Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing knowledge that will help developing diagnostic and therapeutic inventions for human diseases. ..
  27. Polyoma Virus Disrupts ARF Signaling to p53
    Michael Fried; Fiscal Year: 2011
    ..Our goal is to determine the molecular mechanisms underlying ARF signaling to p53, which is dysfunctional in a number of human cancers. ..
  28. Serine/Threonine Phosphatases and Platelet Physiology
    K Vinod Vijayan; Fiscal Year: 2013
    ....
  29. The Regulation of PP1 in the Nucleus
    Rebecca Page; Fiscal Year: 2013
    ..Furthermore, it has the preliminary data that demonstrates that this work will provide unique, novel insights into the molecular regulation of PP1. ..
  30. Role of Protein Phosphatase-1 in Cerebral Ischemia and Cell Death
    Hugh C Hemmings; Fiscal Year: 2013
    ..This approach is targeted to the development of rational mechanism-based protein phosphatase-1 inhibitors to attenuate ischemic cell death and neurological injury. ..
  31. Caveolin 1: a novel modulator of the PP2A/ATM/p53 pathway
    Ferruccio Galbiati; Fiscal Year: 2013
    ....
  32. Intermittent Hypoxia-Induced Inflammation Modulates Respiratory Plasticity
    Jyoti J Watters; Fiscal Year: 2013
    ..Our long-range goal is to harness and promote respiratory plasticity as a therapeutic strategy to treat devastating breathing disorders, such as during cervical spinal injury or motor neuron disease. ..
  33. THE ROLE OF PROTEIN PHOSPHATASE PP2A IN RADIATION INDUCED STEM CELL APOPTOSIS
    GIRDHAR GOPAL SHARMA; Fiscal Year: 2013
    ....
  34. Small Molecule Screen for Apolipoprotein-E/Alzheimer's Disease
    MICHAEL PETER VITEK; Fiscal Year: 2012
    ..This will require several levels of screening to find the few compounds that can be orally administered and show protective activity in the brains of experimental animals. ..
  35. The Role of Tissue Plasminogen Activator in a Mouse Spinal Cord Injury Model
    Noreen Bukhari; Fiscal Year: 2012
    ..We hypothesize that these events are dependent upon DARPP-32 expression. ..
  36. Regulation of Hedgehog signaling at the level of Gli
    Jing Yang; Fiscal Year: 2013
    ..Completion of the above studies will likely uncover an important mechanism of Gli regulation and lead to new therapeutic approaches. ..
  37. Skeletal Muscle Glucose Transport: Exercise and Insulin
    Gregory D Cartee; Fiscal Year: 2013
    ..Completion of the proposed research will provide novel insights into the specific mechanisms that account for improved insulin sensitivity, a major health benefit for both lean and obese individuals. ..
  38. A Testis Specific Regulatory Subunit of Protein Phosphatase-1
    Ann O Sperry; Fiscal Year: 2010
    ..This research will examine the importance of a testis-specific regulatory protein in spermatogenesis and will provide insight into possible remedies for male infertility as well as possible strategies for contraceptive design. ..
  39. Dopamine Signaling Mechanisms of Traumatic Brain Injury
    C Edward Dixon; Fiscal Year: 2013
    ..In survivors, TBI results in the persistent disturbance of cognitive functioning. This project seeks to examine key neurochemical mechanisms underlying cognitive deficits and to evaluate novel therapies to maximize recovery of function. ..
  40. INSULIN-REGULATED MAP KINASE PATHWAYS
    Melanie H Cobb; Fiscal Year: 2013
    ..Finally, the actions of calcineurin (PP2B) and phosphoprotein phosphatase 2A (PP2A) in ligand-specific regulation and function of ERK1/2 will be studied...
  41. Regulation of sperm motility by the Rho signaling pathway
    Daniel W Carr; Fiscal Year: 2012
    ..Successful completion of this proposal will enhance our knowledge of this important regulatory mechanism and thus may facilitate development of treatments for male infertility. ..
  42. Wnt/beta-catenin signaling: phosphorylation regulation of Wnt receptor-Axin inter
    Xi He; Fiscal Year: 2013
    ..Our study will provide better understanding of human embryonic development and pathogenesis of cancer. ..
  43. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
    ....
  44. Mechanisms for Ceramide Mediated Vascular Dysfunction
    JOHN DAVID SYMONS; Fiscal Year: 2012
    ..Our research is focused on determining the mechanisms whereby obesity impairs blood vessel function. We will determine the mechanism whereby the fat metabolite ceramide impairs eNOS enzyme activity and precipitates arterial dysfunction. ..
  45. Guanabenz in the treatment of mutant SOD1 ALS mice
    RAYMOND PHILIP ROOS; Fiscal Year: 2013
    ....
  46. Novel SET Antagonists for the Treatment of Chronic Myelogenous Leukemia
    Dale J Christensen; Fiscal Year: 2013
    ..abstract_text> ..
  47. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    WenHui Wang; Fiscal Year: 2013
    ..The significance of the project is to expand the current understanding regarding the regulation of Na and K transport in the ASDN and to provide an integrated mechanism of WNK4-mediated regulation of ROMK in the ASDN. ..
  48. Biosynthesis of Microbial Polyketides
    David E Cane; Fiscal Year: 2013
    ..Finally, the proposed studies will lead to fundamental new biological insights into the central issue of modern molecular biochemistry, the relationship between protein sequence, structure, and function. ..
  49. Targeting c-Myc and Akt with PP2A reactivation therapy for the treatment of breas
    Dale J Christensen; Fiscal Year: 2013
    ....
  50. Cell cycle regulation by protein phosphatase 2A
    Marc C Mumby; Fiscal Year: 2012
    ..The goals of this proposal are to test the hypothesis that the PR70 subunit of PP2A mediates calcium regulation of G1 progression by controlling the dephosphorylation of the retinoblastoma protein and Cdc6. ..
  51. Mitochondrial Calcium Cycling in Neuronal Function
    Yuriy M Usachev; Fiscal Year: 2010
    ..The proposed studies will advance our understanding of how mitochondrial Ca2+ transporters interplay with protein kinases and phosphatases in neurons to trigger a specific physiological or pathological response. ..
  52. I2PP2A: A Therapeutic Target
    Khalid Iqbal; Fiscal Year: 2013
    ..R. China. ..
  53. Induction and maintenance of mitosis by Cdk1 suppression of Protein phosphatase 1
    ROBERT LEWIS MARGOLIS; Fiscal Year: 2012
    ..This will be a paradigm shift, with the potential of broad implications for understanding the underlying nature of cell cycle mechanisms throughout the cell cycle. ..
  54. Monoamine Transporter Regulation and Antidepressant Activity
    JAMES O DONNELL; Fiscal Year: 2009
    ..abstract_text> ..
  55. Selective Targeting of MEK and AKt in Lymphoma and Myeloma Apoptosis
    Gregory Carey; Fiscal Year: 2009
    ..These studies will ultimately help in the targeting of these pathways to re-sensitize tumors for therapeutic elimination. ..
  56. DUSP1 as a therapeutic target in fibroproliferative acute lung injury
    David W Riches; Fiscal Year: 2013
    ..In addition, DUSP1 may also be a valid therapeutic target in other fibrotic lung disease, e.g. progressive pulmonary fibrosis. ..
  57. Structural and Biochemical Insights into PP2A Holoenzyme Biogenesis
    Yongna Xing; Fiscal Year: 2013
    ....
  58. TROPONIN MODULATION IN HEART FAILURE
    Beata M Wolska; Fiscal Year: 2013
    ..The new mechanism is likely to add to our understanding of heart failure, when pressure and ejection of blood is disturbed. Moreover, the new mechanism may lead to development of novel therapies for heart failure. ..
  59. Regulators of Cdc2/Cdk1
    James E Ferrell; Fiscal Year: 2013
    ....
  60. RESTMD-CHARMM simulation of the Chk2/PP2A interaction in DNA repair
    SHANADEEN C BEGAY; Fiscal Year: 2011
    ..This research will advance cancer care by providing unprecedented insights into the fundamental genetic processes and determinants of breast cancer susceptibility. ..
  61. Phosphoprotein phosphatase 2A, a new target for Alzheimer's Disease interventio
    STEVEN BRAITHWAITE; Fiscal Year: 2010
    ..Successful development of this novel class of phosphoprotein modulators will provide an important additional, and potentially better, therapeutic option for people suffering from AD. ..
  62. Myocardial Ischemia-Reperfusion and Protein Phosphatase 2a
    Polly A Hofmann; Fiscal Year: 2010
    ..the heart, can we improve the short and long term outcomes from ischemic events in the heart? Which of the unique PP2aB targeting subunits is key to improving post-ischemic recovery in the heart, and by what mechanisms does this occur? ..
  63. Novel Screen for Targeted CLL Therapeutics
    Dale Christensen; Fiscal Year: 2009
    ..We now propose to develop a peptide displacement assay that can be used to screen compound libraries to identify small molecule SET antagonists and screen a diverse 30,000 compound library. ..
  64. PROTEIN PHOSPHATASES AND OOCYTE MEIOSIS
    Gary Smith; Fiscal Year: 2002
    ..These studies will provide novel information concerning control of oocyte maturation and spindle formation that may subsequently influence the developmental competency of resulting embryos. ..
  65. IN VITRO MODEL OF PRECONDITIONING WITH ISOLATED MYOCYTES
    CHARLES GANOTE; Fiscal Year: 2001
    ....
  66. PATHOBIOLOGY OF TAU PROTEIN
    KENNETH KOSIK; Fiscal Year: 1999
    ..Saporin is toxic to cells only when it reaches the cytosol. ..
  67. Antiapoptotic Mechanism of Protein Phosphatase-1 in Lens
    David Li; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  68. CARDIAC PHOSPHOPROTEIN PHOSPHATASES
    HENG CHUN LI; Fiscal Year: 1990
    ..The long-term goal of this project is to identify phosphoprotein phosphatase (ptase) isozymes of cardiac muscle and other tissues, and to gain greater understanding of their ..