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. 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
  2. ncbi 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
  3. 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
  4. ncbi 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
  5. 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
  6. 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
  7. 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, , , Switzerland
    Nature 418:970-5. 2002
  8. 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
  9. ncbi 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
  10. ncbi 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

Research Grants

  1. REGULATORY DOMAINS OF PROTEIN PHOSPHATASE 1
    PETER KENNELLY; Fiscal Year: 1999
  2. STRUCTURE, BIOSYNTHESIS AND FUNCTION OF GLYCOPROTEINS
    Stuart Kornfeld; Fiscal Year: 2007
  3. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2010
  4. Regulation of Drosophila arrestins in light adaptation
    Bih Hwa Shieh; Fiscal Year: 2010
  5. Biosynthesis of Microbial Polyketides
    David E Cane; Fiscal Year: 2010
  6. Cardiac Sarcoplasmic Reticulum Calcium Cycling Proteins
    Evangelia G Kranias; Fiscal Year: 2010
  7. Combined neuroprotection and metabolic correction to treat leukodystrophies
    Ernesto Bongarzone; Fiscal Year: 2009
  8. Combined neuroprotection and metabolic correction to treat leukodystrophies
    ERNESTO ROQUE BONGARZONE; Fiscal Year: 2010
  9. PROTEIN PHOSPHATASES AND OOCYTE MEIOSIS
    Gary Smith; Fiscal Year: 2002
  10. Myocardial Ischemia-Reperfusion and Protein Phosphatase 2a
    Polly A Hofmann; Fiscal Year: 2010

Detail Information

Publications280 found, 100 shown here

  1. 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...
  2. ncbi 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
    ....
  3. 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...
  4. ncbi 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...
  5. 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...
  6. 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
    ....
  7. 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, , , 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...
  8. 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...
  9. ncbi 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
    ....
  10. ncbi 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...
  11. ncbi 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...
  12. ncbi 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...
  13. 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...
  14. ncbi Germline mutations in PTEN are present in Bannayan-Zonana syndrome
    D J Marsh
    Nat Genet 16:333-4. 1997
  15. 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...
  16. ncbi 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...
  17. ncbi Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development
    A Faucherre
    Hubrecht Institute, Utrecht, The Netherlands
    Oncogene 27:1079-86. 2008
    ..These pten mutant zebrafish represent a unique model to screen for genetic and/or chemical suppressors of Pten loss-of-function...
  18. ncbi Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1
    J Warmka
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Mol Cell Biol 21:51-60. 2001
    ..Consistent with its role as a negative regulator of Hog1, which accumulates in the nucleus upon activation, Ptc1 was found in both the nucleus and the cytoplasm. Thus, one function of Ptc1 is to inactivate Hog1...
  19. ncbi Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
    O Kassel
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, PO Box 3640, D-76021 Karlsruhe, Germany
    EMBO J 20:7108-16. 2001
    ..These results identify MKP-1 as essential for glucocorticoid-mediated control of Erk-1/2 activation and unravel a novel regulatory mechanism for this anti-inflammatory drug...
  20. ncbi Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells
    Xiaoxing Wang
    Institute of Molecular and Cell Biology, Proteos, Singapore
    J Virol 83:12462-72. 2009
    ..e., blocking PKR activation and inducing GADD34 expression, to maintain de novo protein synthesis in IBV-infected cells and, meanwhile, to enhance viral replication...
  21. ncbi Multiple interactions within the AKAP220 signaling complex contribute to protein phosphatase 1 regulation
    R V Schillace
    Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201 3098, USA
    J Biol Chem 276:12128-34. 2001
    ..These experiments indicate that regulation of PP1 activity by AKAP220 involves a complex network of intra- and intermolecular interactions...
  22. ncbi Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase
    Yong Wu
    Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 282:9777-88. 2007
    ..Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation...
  23. ncbi The scaffolding A/Tpd3 subunit and high phosphatase activity are dispensable for Cdc55 function in the Saccharomyces cerevisiae spindle checkpoint and in cytokinesis
    Roni Koren
    Gonda Center of Molecular Microbiology and The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion Israel Institute of Technology, Bat Galim, Haifa, 31096, Israel
    J Biol Chem 279:48598-606. 2004
    ..This association requires C subunit carboxyl methylation. The residual phosphatase activity associated with Cdc55 in the absence of Tpd3 is sufficient to maintain a partially active spindle checkpoint and to prevent cytokinesis defects...
  24. ncbi Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses
    Hongbo Chi
    Section of Immunobiology, Department of Pharmacology, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 103:2274-9. 2006
    ..These results highlight the complex mechanisms by which the MAPKs regulate innate immunity...
  25. ncbi 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...
  26. 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...
  27. ncbi Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases
    D M Owens
    Cancer Research UK Stress Response Laboratory, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
    Oncogene 26:3203-13. 2007
    ....
  28. ncbi Expression of a protein phosphatase 1 inhibitor, cdNIPP1, increases CDK9 threonine 186 phosphorylation and inhibits HIV-1 transcription
    Tatiana Ammosova
    Center for Sickle Cell Disease, Howard University, Washington, DC 20001, USA
    J Biol Chem 286:3798-804. 2011
    ..Expression of cdNIPP1 as a part of the HIV-1 genome inhibited HIV-1 replication. Our study provides a proof-of-concept for the future development of PP1-targeting compounds as inhibitors of HIV-1 replication...
  29. ncbi Displacement affinity chromatography of protein phosphatase one (PP1) complexes
    Greg B G Moorhead
    Department of Biological Sciences, University of Calgary, 2500 University Dr, NW Calgary, AB T2N 1N4, Canada
    BMC Biochem 9:28. 2008
    ..PP1 is localized to its site of action by interacting with targeting or regulatory proteins, a majority of which contains a primary docking site referred to as the RVXF/W motif...
  30. ncbi Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling
    Y Jiang
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Oncogene 30:3248-60. 2011
    ....
  31. ncbi A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress
    Michael Boyce
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 307:935-9. 2005
    ..More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events...
  32. ncbi Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-1 in Tat-activated HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University, 2121 Georgia Ave, N W Washington, DC 20059, USA
    Retrovirology 2:47. 2005
    ..In the present study we analyze relative contribution of PP2A and PP1 to dephosphorylation of CDK9 and to HIV-1 transcription in vitro and in vivo...
  33. ncbi 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...
  34. ncbi Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor
    Yuichiro Hanyu
    CREST Research Project, Japan Science Technology Corporation, Kyoto, Japan
    Genes Cells 14:539-54. 2009
    ..Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common beta-(Amk2) and gamma-(Cbs2) subunits...
  35. ncbi Nuclear protein phosphatases with Kelch-repeat domains modulate the response to brassinosteroids in Arabidopsis
    Santiago Mora-Garcia
    Plant Biology Labo ato y, The Salk Institute fo Biological Studies, and the Howa d Hughes Medical Institute, La Jolla, Califo nia 92037, USA
    Genes Dev 18:448-60. 2004
    ..Our data indicate that BES1 is subject to antagonistic phosphorylation and dephosphorylation reactions in the nucleus, which fine-tune the amplitude of the response to BL...
  36. ncbi MAPK phosphatases--regulating the immune response
    Yusen Liu
    Center for Perinatal Research, Columbus Children s Research Institute, Columbus Children s Hospital, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43205, USA
    Nat Rev Immunol 7:202-12. 2007
    ..This Review discusses the properties, function and regulation of MKPs during immune responses...
  37. ncbi Protein phosphatases decrease sarcoplasmic reticulum calcium content by stimulating calcium release in cardiac myocytes
    Dmitry Terentyev
    Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-6551, USA
    J Physiol 552:109-18. 2003
    ..Our results suggest that increased intracellular phosphatase activity stimulates RyR-mediated SR Ca2+ release leading to depleted SR Ca2+ stores in cardiac myocytes...
  38. ncbi Generation of active protein phosphatase 2A is coupled to holoenzyme assembly
    Hans Hombauer
    Department of Medical Biochemistry, Max F Perutz Laboratories, Medical University of Vienna, Vienna, Austria
    PLoS Biol 5:e155. 2007
    ..We propose a novel model of PP2A biogenesis in which a tightly controlled activation cascade protects cells from untargeted activity of the free catalytic PP2A subunit...
  39. ncbi Role of host protein tyrosine phosphatase SHP-1 in Leishmania donovani-induced inhibition of nitric oxide production
    Geneviève Forget
    Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Quebec, Canada
    Infect Immun 74:6272-9. 2006
    ....
  40. ncbi Protein phosphatase 2A: variety of forms and diversity of functions
    K Lechward
    Cell and Molecular Signaling Laboratory, , Poland
    Acta Biochim Pol 48:921-33. 2001
    ..Studies on PP2A have shown that this enzyme may be implicated in the regulation of metabolism, transcription, RNA splicing, translation, differentiation, cell cycle, oncogenic transformation and signal transduction...
  41. ncbi 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...
  42. ncbi TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway
    E Jacinto
    Division of Biochemistry, Biozentrum, University of Basel, CH 4056, Basel, Switzerland
    Mol Cell 8:1017-26. 2001
    ....
  43. ncbi Regulation of the TAK1 signaling pathway by protein phosphatase 2C
    M Hanada
    Department of Biochemistry, Institute of Development, Aging, and Cancer, Tohoku University, 4 1 Seiryomachi, Aoba ku, Sendai 980 8575, Japan
    J Biol Chem 276:5753-9. 2001
    ..Collectively, these results indicate that PP2Cbeta negatively regulates the TAK1 signaling pathway by direct dephosphorylation of TAK1...
  44. ncbi Negative regulation of mitosis by the fission yeast protein phosphatase ppa2
    N Kinoshita
    Department of Biophysics, Faculty of Science, Kyoto University, Japan
    Genes Dev 7:1059-71. 1993
    ....
  45. ncbi PPP1R6, a novel member of the family of glycogen-targetting subunits of protein phosphatase 1
    C G Armstrong
    Department of Biochemistry, University of Dundee, Scotland, UK
    FEBS Lett 418:210-4. 1997
    ..The PPP1R6 is associated with glycogen in muscle but is not subject to the same modes of covalent and allosteric regulation as G(M) and G(L)...
  46. ncbi Protein phosphatases take the mitotic stage
    Peter De Wulf
    European Institute of Oncology, Department of Experimental Oncology, IFOM IEO Campus, Milan, Italy
    Curr Opin Cell Biol 21:806-15. 2009
    ..Recent work has now exposed the conserved serine-threonine phosphatases PP1 and PP2A as key regulators of various mitotic processes...
  47. ncbi The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm
    B McCright
    Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, 84112, USA
    J Biol Chem 271:22081-9. 1996
    ..These studies demonstrate an increasing diversity of regulatory mechanisms to control the activity of this key intracellular protein phosphatase and suggest distinct functions for isoforms targeted to different intracellular locations...
  48. ncbi Genetic control of cellular quiescence in S. pombe
    Kenichi Sajiki
    Okinawa Institute of Science and Technology OIST, Initial Research Project, Uruma 904 2234, Okinawa, Japan
    J Cell Sci 122:1418-29. 2009
    ..We propose that the transcriptional role of Fcp1 is central in differentiating quiescence from proliferation...
  49. ncbi Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases
    A N Nguyen
    Section of Microbiology, University of California, Davis, California 95616, USA
    Genes Dev 13:1653-63. 1999
    ..Thus, transient activation of Spc1 upon heat shock is ensured by differential regulation of threonine and tyrosine phosphorylation...
  50. ncbi Multiple protein-aspartate phosphatases provide a mechanism for the integration of diverse signals in the control of development in B. subtilis
    M Perego
    Dipartimento Farmaceutico, Universita degli Studi di Parma, Italy
    Cell 79:1047-55. 1994
    ..The integration of diverse environmental signals that affect the initiation of sporulation likely occurs through the competition between opposing activities of protein kinases and protein phosphatases...
  51. ncbi 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...
  52. ncbi Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation
    J Chen
    Division of Biology and Medicine, Brown University, Providence, RI 02912
    Science 257:1261-4. 1992
    ..Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells...
  53. ncbi The protein phosphatase AtPP2CA negatively regulates abscisic acid signal transduction in Arabidopsis, and effects of abh1 on AtPP2CA mRNA
    Josef M Kuhn
    Division of Biological Sciences, Cell and Developmental Biology Section, and Center for Molecular Genetics, University of California, La Jolla, California 92093 0116, USA
    Plant Physiol 140:127-39. 2006
    ..Moreover, expression of a 35SAtPP2CA cDNA fusion in abh1 partially suppresses abh1 hypersensitivity, and the data further suggest that additional mechanisms contribute to ABA hypersensitivity of abh1...
  54. 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...
  55. ncbi Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits
    S Strack
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Comp Neurol 392:515-27. 1998
    ..Bgamma may target PP2A to cytoskeletal substrates that are important in the establishment and maintenance of neuronal connections...
  56. ncbi Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38
    Marina Lasa
    Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, London W6 8LH, United Kingdom
    Mol Cell Biol 22:7802-11. 2002
    ..These observations suggest that MKP-1 participates in a negative-feedback loop which regulates p38 function and that dexamethasone may inhibit proinflammatory gene expression in part by inducing MKP-1 expression...
  57. ncbi De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1
    Charles E Chalfant
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
    J Biol Chem 277:12587-95. 2002
    ..This is the first report on the dynamic regulation of RNA splicing of members of the Bcl-2 and caspase families in response to regulators of apoptosis...
  58. ncbi Biosynthesis and assembly of capsular polysaccharides in Escherichia coli
    Chris Whitfield
    Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada
    Annu Rev Biochem 75:39-68. 2006
    ..These systems have an impact on both a general understanding of membrane trafficking in bacteria and on bacterial pathogenesis...
  59. ncbi The Arabidopsis ABSCISIC ACID-INSENSITIVE2 (ABI2) and ABI1 genes encode homologous protein phosphatases 2C involved in abscisic acid signal transduction
    J Leung
    Institut des Sciences Vegetales, Centre National de la Recherche Scientifique UPR40, Gif sur Yvette, France
    Plant Cell 9:759-71. 1997
    ..Thus, the homologous ABI1 and ABI2 phosphatases appear to assume partially redundant functions in ABA signaling, which may provide a mechanism to maintain informational homeostasis...
  60. ncbi Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus
    R Visintin
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 398:818-23. 1999
    ..A highly conserved signalling cascade, critical for the exit from mitosis, is required for this movement of Cdc14 during anaphase. Furthermore, we have identified a negative regulator of Cdc14, Cfi1, that anchors Cdc14 in the nucleolus...
  61. ncbi Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex
    W Shou
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Cell 97:233-44. 1999
    ..Nucleolar sequestration may be a general mechanism for the regulation of diverse biological processes...
  62. ncbi 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...
  63. ncbi Phosphorylation-dependent regulation of septin dynamics during the cell cycle
    Jeroen Dobbelaere
    Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Honggerberg, CH 8093, Zurich, Switzerland
    Dev Cell 4:345-57. 2003
    ..Together our results implicate septins in a late step of cytokinesis and indicate that proper regulation of septin dynamics, possibly through the control of their phosphorylation state, is required for the completion of cytokinesis...
  64. ncbi Tau pathology in Alzheimer disease and other tauopathies
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Biochim Biophys Acta 1739:198-210. 2005
    ..Inhibition of this tau abnormality is one of the most promising therapeutic approaches to AD and other tauopathies...
  65. ncbi Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells
    Giovanna Clavarino
    Centre d immunologie de Marseille Luminy, Aix Marseille University, 13288 Marseille, France
    Proc Natl Acad Sci U S A 109:3006-11. 2012
    ..GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways...
  66. ncbi Isoform-specific roles of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca(2+) cycling
    Hidekazu Aoyama
    Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1 1 1 Minami kogushi, Ube, Yamaguchi 755 8505, Japan
    Cardiovasc Res 89:79-88. 2011
    ..We sought to determine the functional contribution of each PP1 isoform to sarcoplasmic reticulum (SR)-mediated Ca(2+) cycling in isolated adult rat cardiomyocytes...
  67. ncbi Inhibition of protein phosphatase 1 by inhibitor-2 exacerbates progression of cardiac failure in a model with pressure overload
    Stephanie Grote-Wessels
    Institut fur Pharmakologie und Toxikologie, Universitatsklinikum Munster, Germany
    Cardiovasc Res 79:464-71. 2008
    ..In this study, we tested the hypothesis whether the inhibitor-2 (I-2) of PP1 can mediate cardiac protection by inhibition of PP1 activity...
  68. ncbi An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein
    Alexander Hirschi
    Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California, USA
    Nat Struct Mol Biol 17:1051-7. 2010
    ..These results provide the first detailed molecular insights into Rb activation and establish a novel mechanism for Rb regulation in which kinase and phosphatase compete for substrate docking...
  69. ncbi Deficiency of protein phosphatase 2A uncouples the nuclear and centrosome cycles and prevents attachment of microtubules to the kinetochore in Drosophila microtubule star (mts) embryos
    H A Snaith
    Department of Biochemistry, University of Dundee, Scotland, UK
    J Cell Sci 109:3001-12. 1996
    ....
  70. ncbi Characterization of the neuronal targeting protein spinophilin and its interactions with protein phosphatase-1
    L C Hsieh-Wilson
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York 10021, USA
    Biochemistry 38:4365-73. 1999
    ..These studies support the notion that spinophilin functions in vivo as a neuronal PP1 targeting subunit by directing the enzyme to postsynaptic densities and regulating its activity toward physiological substrates...
  71. ncbi Alpha4 is an essential regulator of PP2A phosphatase activity
    Mei Kong
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 36:51-60. 2009
    ..These findings demonstrate that alpha4 plays a required role in regulating the assembly and maintenance of adaptive PP2A phosphatase complexes...
  72. ncbi Genetic alterations and expression of the protein phosphatase 1 genes in human cancers
    S Takakura
    Biology Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
    Int J Oncol 18:817-24. 2001
    ..In contrast, differential expression, somatic mutations and/or genetic polymorphisms of several regulatory subunit genes indicate the involvement of these genes in multistep carcinogenesis...
  73. ncbi 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...
  74. ncbi Protein tyrosine phosphatases: mechanisms of catalysis and regulation
    J M Denu
    Oregon Health Sciences University, Department of Biochemistry and Molecular Biology, Portland 97201 3098, USA
    Curr Opin Chem Biol 2:633-41. 1998
    ..In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular interactions, whereby inhibition is mediated by sterically blocking the active-site cleft...
  75. ncbi A novel glycogen-targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents
    Shonagh Munro
    Medical Research Council Protein Phosphorylation Unit, University of Dundee, UK
    FEBS J 272:1478-89. 2005
    ..The observations imply that the mechanisms by which insulin regulates glycogen synthesis in liver and skeletal muscle are different in rodents and humans...
  76. ncbi ABA-Hypersensitive Germination1 encodes a protein phosphatase 2C, an essential component of abscisic acid signaling in Arabidopsis seed
    Noriyuki Nishimura
    Laboratory of Environmental Molecular Biology, RIKEN Wako Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Plant J 50:935-49. 2007
    ..In addition, the ahg1-1 ahg3-1 double mutant was more hypersensitive than either monogenic mutant. These results suggest that AHG1 has specific functions in seed development and germination, shared partly with AHG3...
  77. ncbi The extracellular Phr peptide-Rap phosphatase signaling circuit of Bacillus subtilis
    Mridula Pottathil
    Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, 1602 Molecular Sciences Building, 405 Hilgard Avenue, Los Angeles, CA 90095, USA
    Front Biosci 8:d32-45. 2003
    ..e. the response to high cell density). This review will address the mechanism of extracellular Phr signaling peptide production, transport, response, and their role in quorum sensing...
  78. ncbi PTC1 is required for vacuole inheritance and promotes the association of the myosin-V vacuole-specific receptor complex
    Yui Jin
    Life Sciences Institute, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 2216, USA
    Mol Biol Cell 20:1312-23. 2009
    ..Moreover, these observations suggest that despite the existence of organelle-specific receptors, there is a higher order regulation that coordinates the movement of diverse cellular components...
  79. ncbi The type 2C protein phosphatase FgPtc1p of the plant fungal pathogen Fusarium graminearum is involved in lithium toxicity and virulence
    Linghuo Jiang
    State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100094, China
    Mol Plant Pathol 11:277-82. 2010
    ..Furthermore, we showed that deletion of FgPTC1 attenuated the virulence of F. graminearum on wheat. Therefore, FgPTC1 plays an important role in regulating the hyphal growth and virulence of F. graminearum...
  80. ncbi Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival
    Ruth Tal
    Department of Biochemistry and Food Science, Faculty of Agricultural, Food, and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
    J Biol Chem 282:5617-24. 2007
    ..Our data suggest that Aup1p may be part of a signal transduction mechanism that marks mitochondria for sequestration into autophagosomes...
  81. ncbi Regional expression of protein phosphatase type 1 and 2A catalytic subunit isoforms in the human heart
    H Luss
    Institut fur Pharmakologie und Toxikologie, Westfalische Wilhelms Universitat Munster, Germany
    J Mol Cell Cardiol 32:2349-59. 2000
    ..Thus, lower protein expression of PP2A in atrium could contribute to the faster relaxation by increasing the phosphorylation state of TnI. We conclude that expression of PP1 and PP2A isoforms is regionally regulated in the human heart...
  82. ncbi Control of the terminal step of intracellular membrane fusion by protein phosphatase 1
    C Peters
    Friedrich Miescher Laboratorium, Spemannstrasse 37 39, 72076 Tubingen, Germany
    Science 285:1084-7. 1999
    ..The PP1-calmodulin complex was required at multiple sites of intracellular trafficking; hence, PP1 may be a general factor controlling membrane bilayer mixing...
  83. ncbi Dual-specificity phosphatases: critical regulators with diverse cellular targets
    Kate I Patterson
    Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst 2010, Sydney, NSW, Australia
    Biochem J 418:475-89. 2009
    ..The present review provides an overview of the DUSP family before focusing on atypical DUSPs, emerging as a group of proteins with vastly diverse substrate specificity and function...
  84. ncbi IPP5, a novel protein inhibitor of protein phosphatase 1, promotes G1/S progression in a Thr-40-dependent manner
    Xiaojian Wang
    Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China
    J Biol Chem 283:12076-84. 2008
    ..Our findings suggest that IPP5, by acting as an inhibitory molecule for PP1, can promote tumor cell growth and cell cycle progression, and may be a promising target in cancer therapeutics in IPP5-highly expressing tumor cells...
  85. ncbi Protein phosphatase 1 regulates the stability of the circadian protein PER2
    Monica Gallego
    Center for Children, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
    Biochem J 399:169-75. 2006
    ..Over-expression of the PP1 inhibitors, protein phosphatase 1 holoenzyme inhibitor-1 and Inhibitor-2, confirmed these results. Thus PP1 regulates PER2 stability and is therefore a candidate to regulate mammalian circadian rhythms...
  86. 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...
  87. ncbi Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib
    Wen Hsin Chang
    Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Center for Excellence in Environmental Medicine, Kaohsiung, Taiwan
    Cancer Res 71:383-92. 2011
    ..Our findings suggest that amiloride may offer a potential treatment option for chronic myelogenous leukemia either alone or in combination with imatinib...
  88. ncbi Differential expression of protein phosphatase 1 isoforms in mammalian brain
    E F da Cruz e Silva
    Rockefeller University, New York, New York 10021, USA
    J Neurosci 15:3375-89. 1995
    ..PP1 beta appeared to be relatively less abundant in the same cells, as judged both by "in situ" hybridization and by the apparent absence of PP1 beta clones from the striatal cDNA libraries used...
  89. ncbi PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ
    Chen Ying Liu
    Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology School of Medicine, Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
    J Biol Chem 286:5558-66. 2011
    ..As a result, PP1 and ASPP2 increase TAZ-dependent gene expression. This study demonstrates that PP1A and ASPP2 play a critical role in promoting TAZ function by antagonizing the LATS kinase through TAZ dephosphorylation...
  90. ncbi Genome-wide and expression analysis of protein phosphatase 2C in rice and Arabidopsis
    Tongtong Xue
    State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong 271018, PR China
    BMC Genomics 9:550. 2008
    ..A genome-wide overview of the PP2C gene family in plants is not yet available...
  91. ncbi Protein phosphatase 4 mediates localization of the Miranda complex during Drosophila neuroblast asymmetric divisions
    Rita Sousa-Nunes
    Department of Biological Sciences, Temasek Life Sciences Laboratory, National University of Singapore, Singapore
    Genes Dev 23:359-72. 2009
    ..Our findings suggest that Flfl may target PP4 to the MIra protein complex to facilitate dephosphorylation step(s) crucial for its cortical association/asymmetric localization...
  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 Modulation of cell wall structure and antimicrobial susceptibility by a Staphylococcus aureus eukaryote-like serine/threonine kinase and phosphatase
    Amanda M Beltramini
    Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH 43210, USA
    Infect Immun 77:1406-16. 2009
    ..Together, these results indicate that S. aureus STK- and STP-mediated reversible phosphorylation reactions play a critical role in proper cell wall architecture, and thus the modulation of antimicrobial resistance, in S. aureus...
  94. ncbi Protein phosphatase 1 regulates the histone code for long-term memory
    Kyoko Koshibu
    Brain Research Institute, University of Zurich, Swiss Federal Institute of Technology, CH 8057 Zurich, Switzerland
    J Neurosci 29:13079-89. 2009
    ..Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1...
  95. ncbi ABI1 of Arabidopsis is a protein serine/threonine phosphatase highly regulated by the proton and magnesium ion concentration
    M P Leube
    Institut für Pflanzenwissenschaften, Eidgenossische Technische Hochschule Zurich, Switzerland
    FEBS Lett 424:100-4. 1998
    ....
  96. ncbi Protein phosphatase 2A activates the proapoptotic function of BAD in interleukin- 3-dependent lymphoid cells by a mechanism requiring 14-3-3 dissociation
    C W Chiang
    Department of Pediatrics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Blood 97:1289-97. 2001
    ..12 cells expressing wild-type BAD but not phosphorylation-defective mutant BAD. These data indicate that PP2A, or a PP2A-like enzyme, dephosphorylates BAD and, in conjunction with 14-3-3, modulates cytokine-mediated survival...
  97. ncbi MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?
    A R Clark
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom
    J Endocrinol 178:5-12. 2003
    ..The potential relevance of MKP-1 to some of the biological effects of GCs is discussed...
  98. ncbi Stress-induced protein phosphatase 2C is a negative regulator of a mitogen-activated protein kinase
    Irute Meskiene
    Institute of Microbiology and Genetics, Vienna Biocenter, Dr Bohrgasse 9, A 1030 Vienna, Austria
    J Biol Chem 278:18945-52. 2003
    ..Wound-induced MP2C expression correlates with the time window when SIMK is inactivated, corroborating the notion that MP2C is involved in resetting the SIMK signaling pathway...
  99. 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
    ....
  100. ncbi 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...
  101. ncbi Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock
    Michael Hammer
    Institute of Medical Microbiology, Immunology, and Hygiene, Technical University Munich, 81675 Munich, Germany
    J Exp Med 203:15-20. 2006
    ..These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock...

Research Grants81

  1. REGULATORY DOMAINS OF PROTEIN PHOSPHATASE 1
    PETER KENNELLY; Fiscal Year: 1999
    ..Successful completion of this project may increase the understanding of how PP1 is regulated in cells, and do so in molecular detail. ..
  2. STRUCTURE, BIOSYNTHESIS AND FUNCTION OF GLYCOPROTEINS
    Stuart Kornfeld; Fiscal Year: 2007
    ..If it is novel, we will clone it to obtain its sequence and identify protein domains that may give clues as to its function. We will then study how the protein facilitates AP-1 recruitment...
  3. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2010
    ..This proposal will advance public health by determining how PP2A, the primary eukaryotic serine/threonine phosphatase, alters the injurious responses to cigarette smoke exposure in the lung. ..
  4. Regulation of Drosophila arrestins in light adaptation
    Bih Hwa Shieh; Fiscal Year: 2010
    ..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. ..
  5. Biosynthesis of Microbial Polyketides
    David E Cane; Fiscal Year: 2010
    ..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. ..
  6. Cardiac Sarcoplasmic Reticulum Calcium Cycling Proteins
    Evangelia G Kranias; Fiscal Year: 2010
    ..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. ..
  7. Combined neuroprotection and metabolic correction to treat leukodystrophies
    Ernesto Bongarzone; Fiscal Year: 2009
    ....
  8. Combined neuroprotection and metabolic correction to treat leukodystrophies
    ERNESTO ROQUE BONGARZONE; Fiscal Year: 2010
    ....
  9. 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. ..
  10. 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? ..
  11. Mitogen-activated Protein Kinases and NF-kB Activation in Vascular Smooth Muscle
    Bingbing Jiang; Fiscal Year: 2009
    ....
  12. Mitogen-activated Protein Kinases and NF-kB Activation in Vascular Smooth Muscle
    Bingbing Jiang; Fiscal Year: 2010
    ....
  13. Induction and maintenance of mitosis by Cdk1 suppression of Protein phosphatase 1
    ROBERT LEWIS MARGOLIS; Fiscal Year: 2010
    ..If our hypothesis is true, our discovery will profoundly change understanding of mitotic control, and thus reveal new targets for cancer chemotherapy. ..
  14. IN VITRO MODEL OF PRECONDITIONING WITH ISOLATED MYOCYTES
    CHARLES GANOTE; Fiscal Year: 2001
    ....
  15. Phosphorylation & Function of Inhibitor-2
    David L Brautigan; Fiscal Year: 2010
    ..The goal is to understand how this protein acts to connect multiple signaling inputs into centrosome actions. Understanding cellular mechanisms is the basis for diagnosis and treatment of human diseases. ..
  16. Phosphorylation & Function of Inhibitor-2
    DAVID BRAUTIGAN; Fiscal Year: 2009
    ..The goal is to understand how this protein acts to connect multiple signaling inputs into centrosome actions. Understanding cellular mechanisms is the basis for diagnosis and treatment of human diseases. ..
  17. Small Molecule Screen for Apolipoprotein-E/Alzheimer's Disease
    MICHAEL PETER VITEK; Fiscal Year: 2010
    ..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. ..
  18. Role of Protein Phosphatase-1 in Cerebral Ischemia and Cell Death
    Hugh C Hemmings; Fiscal Year: 2010
    ..This approach is targeted to the development of rational mechanism-based protein phosphatase-1 inhibitors to attenuate ischemic cell death and neurological injury. ..
  19. Role of Protein Phosphatase-1 in Cerebral Ischemia and Cell Death
    HUGH HEMMINGS; Fiscal Year: 2009
    ..This approach is targeted to the development of rational mechanism-based protein phosphatase-1 inhibitors to attenuate ischemic cell death and neurological injury. ..
  20. 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. ..
  21. Caveolin 1: a novel modulator of the PP2A/ATM/p53 pathway
    Ferruccio Galbiati; Fiscal Year: 2010
    ....
  22. Role of Protein Phosphatase-1 in Cerebral Ischemia and Cell Death
    HUGH HEMMINGS; Fiscal Year: 2009
    ..This approach is targeted to the development of rational mechanism-based protein phosphatase-1 inhibitors to attenuate ischemic cell death and neurological injury. ..
  23. 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. ..
  24. Antiapoptotic Mechanism of Protein Phosphatase-1 in Lens
    David Li; Fiscal Year: 2007
    ....
  25. Differential Regulation of Na-K-Cl Cotransport
    Carole M Liedtke; Fiscal Year: 2010
    ..More importantly, the studies will lay the foundation for predicting and testing the effects of drugs, both pharmaceutical and recreational, that alter NKCC1 function. ..
  26. GDP/GTP Exchange Factors: Nucleus Accumbens Plasticity
    ELIZABETH EIPPER; Fiscal Year: 2007
    ..PP-1, a DARPP-32 target localized to spines, also binds to Kalirin. It is our hypothesis that Kalirin-7, through its interactions with these regulators, integrates the effects of diverse signaling pathways on spine formation. ..
  27. Reversible phosphorylation in Hedgehog signaling
    ALAN ZHU; Fiscal Year: 2010
    ....
  28. Reversible phosphorylation in Hedgehog signaling
    ALAN ZHU; Fiscal Year: 2010
    ....
  29. Reversible phosphorylation in Hedgehog signaling
    ALAN ZHU; Fiscal Year: 2009
    ....
  30. Cellular Targets of Polyomavirus Tumor Antigens
    DAVID PALLAS; Fiscal Year: 2009
    ..Drugs that function at the level of this new target would likely be less toxic, and therefore more useful for anti-cancer therapy. ..
  31. Cellular Targets of Polyomavirus Tumor Antigens
    DAVID PALLAS; Fiscal Year: 2009
    ..Drugs that function at the level of this new target would likely be less toxic, and therefore more useful for anti-cancer therapy. ..