enzyme activation

Summary

Summary: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

Top Publications

  1. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  3. ncbi Mammalian MAP kinase signalling cascades
    L Chang
    Department of Pharmacology, University of California San Diego, La Jolla 92093-0636, USA
    Nature 410:37-40. 2001
  4. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
  5. ncbi Cryopyrin activates the inflammasome in response to toxins and ATP
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 440:228-32. 2006
  6. ncbi Rho GTPases and the actin cytoskeleton
    A Hall
    Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group, University College London, Gower Street, London WC1E 6BT, UK
    Science 279:509-14. 1998
  7. pmc The selectivity of protein kinase inhibitors: a further update
    Jenny Bain
    Division of Signal Transduction Therapy, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 408:297-315. 2007
  8. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
  9. ncbi Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    D A Cross
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Nature 378:785-9. 1995
  10. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003

Detail Information

Publications317 found, 100 shown here

  1. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
    ..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation...
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  3. ncbi Mammalian MAP kinase signalling cascades
    L Chang
    Department of Pharmacology, University of California San Diego, La Jolla 92093-0636, USA
    Nature 410:37-40. 2001
    ....
  4. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders...
  5. ncbi Cryopyrin activates the inflammasome in response to toxins and ATP
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 440:228-32. 2006
    ..Therefore, cryopyrin is essential for inflammasome activation in response to signalling pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L. monocytogenes...
  6. ncbi Rho GTPases and the actin cytoskeleton
    A Hall
    Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group, University College London, Gower Street, London WC1E 6BT, UK
    Science 279:509-14. 1998
    ....
  7. pmc The selectivity of protein kinase inhibitors: a further update
    Jenny Bain
    Division of Signal Transduction Therapy, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 408:297-315. 2007
    ..Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes...
  8. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
    ..Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity...
  9. ncbi Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    D A Cross
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Nature 378:785-9. 1995
    ..Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase...
  10. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  11. ncbi Integrin-regulated FAK-Src signaling in normal and cancer cells
    Satyajit K Mitra
    The Scripps Research Institute, Department of Immunology, IMM21 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 18:516-23. 2006
    ....
  12. ncbi Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases
    Gary L Johnson
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Science 298:1911-2. 2002
    ..The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity...
  13. ncbi The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
    Fabio Martinon
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Mol Cell 10:417-26. 2002
    ..Thus, the inflammasome constitutes an important arm of the innate immunity...
  14. ncbi Apoptosis: controlled demolition at the cellular level
    Rebecca C Taylor
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Nat Rev Mol Cell Biol 9:231-41. 2008
    ..These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules...
  15. ncbi Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta
    T Nakagawa
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:98-103. 2000
    ..Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity...
  16. ncbi Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
    D R Alessi
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland
    Curr Biol 7:261-9. 1997
    ..The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown...
  17. ncbi Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function
    O Adachi
    Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan
    Immunity 9:143-50. 1998
    ..Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor...
  18. pmc AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
    Veit Hornung
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 458:514-8. 2009
    ..Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1...
  19. pmc The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 310:1642-6. 2005
    ..Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels...
  20. ncbi The nuts and bolts of AGC protein kinases
    Laura R Pearce
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Nat Rev Mol Cell Biol 11:9-22. 2010
    ..In addition, AGC kinases mediate diverse and important cellular functions, and their mutation and/or dysregulation contributes to the pathogenesis of many human diseases, including cancer and diabetes...
  21. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  22. ncbi Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
    P Li
    Howard Hughes Medical Institute, and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 91:479-89. 1997
    ....
  23. ncbi Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
    S Dimmeler
    Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany
    Nature 399:601-5. 1999
    ..Thus, phosphorylation of eNOS by Akt represents a novel Ca2+-independent regulatory mechanism for activation of eNOS...
  24. ncbi An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
    Xuewu Zhang
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
    Cell 125:1137-49. 2006
    ..The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization...
  25. ncbi Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
    A Bertolotti
    Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    Nat Cell Biol 2:326-32. 2000
    ..These findings are consistent with a model in which BiP represses signalling through PERK and IRE1 and protein misfolding relieves this repression by effecting the release of BiP from the PERK and IRE1 lumenal domains...
  26. pmc The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3329-35. 2004
    ..The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics...
  27. ncbi Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 430:213-8. 2004
    ..Notably, cell death triggered by stimuli that engage caspase-1 was ablated in macrophages lacking either ASC or Ipaf, suggesting a coupling between the inflammatory and cell death pathways...
  28. ncbi Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases
    Hideaki Kamata
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 120:649-61. 2005
    ..Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration...
  29. pmc Mechanism of activation of protein kinase B by insulin and IGF-1
    D R Alessi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    EMBO J 15:6541-51. 1996
    ..We propose a model whereby PKBalpha becomes phosphorylated and activated in insulin/IGF-1-stimulated cells by an upstream kinase(s)...
  30. pmc Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
    ..We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta...
  31. ncbi Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition
    C Du
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 102:33-42. 2000
    ..Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases...
  32. ncbi Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)
    M Amano
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 01
    J Biol Chem 271:20246-9. 1996
    ..The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction...
  33. ncbi Akt stimulates aerobic glycolysis in cancer cells
    Rebecca L Elstrom
    Department of Cancer Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Cancer Res 64:3892-9. 2004
    ....
  34. pmc SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
    Michelle Pacholec
    Department of Cardiovascular, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    J Biol Chem 285:8340-51. 2010
    ..Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1...
  35. 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
    ....
  36. ncbi Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase
    M Maekawa
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606 8315, Japan
    Science 285:895-8. 1999
    ..These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton...
  37. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  38. ncbi Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase
    Simon A Hawley
    Division of Molecular Physiology University of Dundee, Dundee, Scotland, United Kingdom
    Cell Metab 2:9-19. 2005
    ..Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta...
  39. ncbi Src family kinases in tumor progression and metastasis
    Justin M Summy
    The University of Texas M D Anderson Cancer Center, Department of Cancer Biology, Houston, TX 77030, USA
    Cancer Metastasis Rev 22:337-58. 2003
    ..Given the ability of Src and its family members to participate in so many aspects of tumor progression and metastasis, Src family kinases are attractive targets for future anti-cancer therapeutics...
  40. ncbi An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9
    H Zou
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
    J Biol Chem 274:11549-56. 1999
    ..The stoichiometric ratio of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated, caspase-9 disassociates from the complex and becomes available to cleave and activate downstream caspases such as caspase-3...
  41. ncbi Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states
    Yun S Lee
    Department of Biological Sciences, Seoul National University, San 56 1, Sillim dong, Kwanak gu, Korea
    Diabetes 55:2256-64. 2006
    ..These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity...
  42. ncbi Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action
    Kenta Hara
    Biosignal Research Center, Kobe University, 657 8501, Kobe, Japan
    Cell 110:177-89. 2002
    ..elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo...
  43. pmc How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer?
    Yohannes Mebratu
    Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, USA
    Cell Cycle 8:1168-75. 2009
    ..Studies that further define the function of cytosolic ERK1/2 and its cytosolic substrates that enhance cell death will be essential to harness this pathway for developing effective treatments for cancer and chronic inflammatory diseases...
  44. ncbi Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington 98103, USA
    Nat Immunol 7:569-75. 2006
    ....
  45. ncbi The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition
    S Meloche
    Departments of Pharmacology and Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Universite de Montreal, Montreal, Quebec, Canada
    Oncogene 26:3227-39. 2007
    ..In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies...
  46. ncbi Non-Smad TGF-beta signals
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    J Cell Sci 118:3573-84. 2005
    ....
  47. pmc Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1
    M Saitoh
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    EMBO J 17:2596-606. 1998
    ..The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine- and stress-induced apoptosis...
  48. pmc Orchestrating the unfolded protein response in health and disease
    Randal J Kaufman
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109 0650, USA
    J Clin Invest 110:1389-98. 2002
  49. ncbi LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Curr Biol 13:2004-8. 2003
    ..These results identify a link between two protein kinases, previously thought to lie in unrelated, distinct pathways, that are associated with human diseases...
  50. ncbi Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways
    H Ichijo
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    Science 275:90-4. 1997
    ..Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis...
  51. ncbi Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms
    A Bonni
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 286:1358-62. 1999
    ....
  52. ncbi The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs
    Tencho Tenev
    The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Mol Cell 43:432-48. 2011
    ..Together, our observations shed new light on fundamental mechanisms by which chemotherapeutics may kill cancer cells...
  53. ncbi Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
    L del Peso
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 278:687-9. 1997
    ..Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway...
  54. ncbi AMP-activated protein kinase in metabolic control and insulin signaling
    Mhairi C Towler
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    Circ Res 100:328-41. 2007
    ..It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome...
  55. pmc Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner
    E A Slee
    Molecular Cell Biology Laboratory, Department of Biology, National University of Ireland, Maynooth, Co Kildare, Ireland
    J Cell Biol 144:281-92. 1999
    ..Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9...
  56. ncbi Mechanisms of caspase activation
    Kelly M Boatright
    Program in Cell Death and Apoptosis Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 15:725-31. 2003
    ..This mechanism is proximity-induced dimerization without cleavage, and its elucidation has led to the revision of concepts of feedback regulation of apoptosis...
  57. ncbi Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages
    Luigi Franchi
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nat Immunol 7:576-82. 2006
    ..Thus, detection of flagellin through Ipaf induces caspase-1 activation independently of Toll-like receptor 5 in salmonella-infected and lipopolysaccharide-tolerized macrophages...
  58. ncbi Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome
    Barbara Cool
    Department of Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    Cell Metab 3:403-16. 2006
    ..These results demonstrate that small molecule-mediated activation of AMPK in vivo is feasible and represents a promising approach for the treatment of type 2 diabetes and the metabolic syndrome...
  59. ncbi AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
    R H Medema
    Department of Hematology, University Medical Center, Utrecht, The Netherlands
    Nature 404:782-7. 2000
    ..We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation...
  60. ncbi The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases
    Rebecca L Hurley
    Departments of Medicine and Biochemistry, Dartmouth Medical School and the Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
    J Biol Chem 280:29060-6. 2005
    ..These data indicate that the CaMKKs function in intact cells as AMPKKs, predicting wider roles for these kinases in regulating AMPK activity in vivo...
  61. ncbi Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor
    Seong Woon Yu
    Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Science 297:259-63. 2002
    ..These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death...
  62. ncbi The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes
    J E Ferrell
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305 5332, USA
    Science 280:895-8. 1998
    ..These findings provide a biochemical rationale for the all-or-none character of this cell fate switch...
  63. ncbi Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
    J Yang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Science 275:1129-32. 1997
    ..Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria...
  64. ncbi NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase
    O N Ozes
    Department of Microbiology and Immunology, Indiana University School of Medicine, The Walther Oncology Center, Indianapolis 46202, USA
    Nature 401:82-5. 1999
    ..Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappaB. These findings indicate that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses...
  65. ncbi Mammalian caspases: structure, activation, substrates, and functions during apoptosis
    W C Earnshaw
    Institute of Cell and Molecular Biology, University of Edinburgh, Scotland, United Kingdom
    Annu Rev Biochem 68:383-424. 1999
    ..Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death...
  66. ncbi Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Cell Metab 2:21-33. 2005
    ..These results demonstrate that AMPK is regulated by at least two upstream kinases and suggest that AMPK may play a role in Ca(2+)-mediated signal transduction pathways...
  67. ncbi Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression
    Jiyong Liang
    Molecular and Cell Biology, Sunnybrook and Women s Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
    Cell Cycle 2:339-45. 2003
    ..The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control...
  68. pmc Structure of mammalian AMPK and its regulation by ADP
    Bing Xiao
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nature 472:230-3. 2011
    ..From our biochemical and structural data we develop a model for how the energy status of a cell regulates AMPK activity...
  69. ncbi Activation and signaling of the p38 MAP kinase pathway
    Tyler Zarubin
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Res 15:11-8. 2005
    ..Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38...
  70. pmc The decision to enter mitosis: feedback and redundancy in the mitotic entry network
    Arne Lindqvist
    Department of Medical Oncology, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands
    J Cell Biol 185:193-202. 2009
    ....
  71. ncbi Src kinases as therapeutic targets for cancer
    Lori C Kim
    University of South Florida College of Medicine, Tampa, FL, USA
    Nat Rev Clin Oncol 6:587-95. 2009
    ..In preclinical studies these agents can suppress tumor growth and metastases. The agents seem to be safe in humans and could add to the therapeutic arsenal against subsets of cancers...
  72. ncbi The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase
    T F Franke
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cell 81:727-36. 1995
    ..These results identify Akt as a novel target of PI 3-kinase and suggest that the Akt PH domain may be a mediator of PI 3-kinase signaling...
  73. ncbi JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
    B Derijard
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605
    Cell 76:1025-37. 1994
    ..Thus, JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation. These properties indicate that JNK1 activation may play an important role in tumor promotion...
  74. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains...
  75. pmc Ras oncogenes: split personalities
    Antoine E Karnoub
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 9:517-31. 2008
    ....
  76. ncbi Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation
    H P Gerber
    Department of Cardiovascular Research, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 273:30336-43. 1998
    ..Inhibition of apoptosis may represent a major aspect of the regulatory activity of VEGF on the vascular endothelium...
  77. pmc SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase
    Xiuyun Hou
    Vascular Biology Unit and Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, and Section of Endocrinology, Boston University, Boston, MA 02118, USA
    J Biol Chem 283:20015-26. 2008
    ..Targeting SIRT1/LKB1/AMPK signaling by polyphenols may have potential therapeutic implications for dyslipidemia and accelerated atherosclerosis in diabetes and age-related diseases...
  78. pmc Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B
    Alexander E Kelly
    Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA
    Science 330:235-9. 2010
    ..These findings establish a direct cellular role for mitotic histone H3T3 phosphorylation, which is read and translated by the CPC to ensure accurate cell division...
  79. pmc AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
    Carles Canto
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
    Nature 458:1056-60. 2009
    ..The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism...
  80. ncbi TNF-alpha induces two distinct caspase-8 activation pathways
    Lai Wang
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 133:693-703. 2008
    ..These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP...
  81. pmc AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer
    Krishna M Vasudevan
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 16:21-32. 2009
    ..Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations...
  82. ncbi Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer
    R Katso
    Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1W 7BS, England
    Annu Rev Cell Dev Biol 17:615-75. 2001
    ..The evidence for the role of deregulated PI3K signaling in diseases such as cancer and diabetes is reviewed...
  83. ncbi An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior
    Jean Martin Beaulieu
    Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cell 122:261-73. 2005
    ....
  84. ncbi Mechanisms of cytochrome c release from mitochondria
    C Garrido
    INSERM U517, Faculty of Medicine and Pharmacy, F 21033 Dijon, France
    Cell Death Differ 13:1423-33. 2006
    ..This review deals with the events involved in Cyt c release from mitochondria, with special attention to its regulation and final consequences...
  85. ncbi Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
    Chee Kwee Ea
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 22:245-57. 2006
    ..These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation...
  86. pmc ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions
    Philippe P Roux
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Microbiol Mol Biol Rev 68:320-44. 2004
    ..In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries...
  87. ncbi Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway
    C Tournier
    Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 288:870-4. 2000
    ..These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway...
  88. ncbi Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes
    L M Luttrell
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 283:655-61. 1999
    ....
  89. ncbi Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf
    Amal Amer
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 281:35217-23. 2006
    ..These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium...
  90. ncbi p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain
    Shan Xue Jin
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci 23:4017-22. 2003
    ..Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain...
  91. ncbi Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
    Libor Macurek
    Department of Medical Oncology, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands
    Nature 455:119-23. 2008
    ..Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A...
  92. ncbi The stress-activated protein kinase subfamily of c-Jun kinases
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, Charlestown 02129
    Nature 369:156-60. 1994
    ..9). SAPKs therefore define a new TNF-alpha and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun...
  93. pmc Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis
    Edward J McManus
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, Scotland
    EMBO J 24:1571-83. 2005
    ..These results establish the function of Ser21/Ser9 phosphorylation in several processes in which GSK3 inactivation has previously been implicated...
  94. ncbi PKB/AKT: functional insights from genetic models
    M P Scheid
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Nat Rev Mol Cell Biol 2:760-8. 2001
    ....
  95. ncbi TopBP1 activates the ATR-ATRIP complex
    Akiko Kumagai
    Division of Biology 216 76, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 124:943-55. 2006
    ..These studies establish that activation of ATR by TopBP1 is a crucial step in the initiation of ATR-dependent signaling processes...
  96. pmc Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages
    Mihai G Netea
    Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA
    Blood 113:2324-35. 2009
    ..We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation...
  97. pmc Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
    M Delcommenne
    British Columbia Cancer Agency, Jack Bell Research Centre, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6 Canada
    Proc Natl Acad Sci U S A 95:11211-6. 1998
    ..ILK is thus a receptor-proximal effector for the Pi(3)K-dependent, extracellular matrix and growth factor mediated, activation of PKB/AKT, and inhibition of GSK-3...
  98. ncbi Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
    G Levkowitz
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell 4:1029-40. 1999
    ..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways...
  99. ncbi Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice
    E C Holland
    Department of Neurosurgery, MD Anderson Cancer Center, Houston, Texas, USA
    Nat Genet 25:55-7. 2000
    ..11), and we show here that Akt activity is increased in most of these tumours, implying that combined activation of these two pathways accurately models the biology of this disease...
  100. ncbi Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release
    J Whitfield
    Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, WC1E 6BT, London, United Kingdom
    Neuron 29:629-43. 2001
    ....
  101. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
    ..Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state...

Research Grants62

  1. Cyclic AMP Signaling in Pseudomonas aeruginosa Virulence
    Matthew C Wolfgang; Fiscal Year: 2011
    ..Preliminary results indicate that the MASE2 domain is required for enzyme activation. 2) Investigate the mechanism and biological significance of inorganic carbon (bicarbonate and CO2)-..
  2. FRET-based Biosensors to Monitor Redox in Cell Cycle Regulation
    Paul J A Kenis; Fiscal Year: 2012
    ..cellular processes that regulate the balance between proliferation and cell death, including DNA synthesis, enzyme activation, cell cycle progression, proliferation, differentiation, and apoptosis...
  3. Biochemical Basis of Somatic Hypermutation
    MYRON GOODMAN; Fiscal Year: 2013
    ....
  4. Soluble guanylyl cyclase modulation by endogenous elements and exogenous factors
    Emil Martin; Fiscal Year: 2012
    ..mechanisms that govern the function of this enzyme, including specific ligand selection and NO induced enzyme activation. This proposal will provide incisive insight into the biophysical and biochemical specifics of NO-dependent ..
  5. Alcohol abuse and Endoplasmic Reticulum dysfunction in exocrine pancreas
    Aurelia Lugea; Fiscal Year: 2013
    ..and promote its propagation into pathophysiologic features of pancreatitis including aberrant digestive enzyme activation and acinar cell death...
  6. Structure and Function of the SAGA Deubiquitinating Module
    Cynthia Wolberger; Fiscal Year: 2013
    ..intertwined arrangement of DUB module subunits and now sets the stage for detailed investigations into enzyme activation and targeting to histones. Aim 1 addresses how Ubp8 is activated by the other DUB subunits...
  7. B Cell Expressed COX2 and AID Dependent Sjogrens Syndrome Autoimmunity
    PATRICIA K MONGINI; Fiscal Year: 2013
    ....
  8. Mechanisms Underlying Colorectal Cancer Risk in IBD (PQ6)
    Laura P Hale; Fiscal Year: 2013
    ..Recent research has shown that the expression of the mutation-inducing enzyme activation-induced cytidine deaminase (AID) is induced by colon inflammation and that AID expression can enhance the ..
  9. Nitroxyl and Nitric Oxide Producing Reactions of Hydroxyurea and Related Compound
    S Bruce King; Fiscal Year: 2010
    ..the kinetics, reaction products and structural requirements of these reactions as well as the extent of enzyme activation/inhibition;ii) to determine whether C-nitroso compounds act as NO/HNO donors by preparing and characterizing ..
  10. Chiroptical Induced CPL-Based Tool as a Probe of Biological Substrates
    Gilles Muller; Fiscal Year: 2013
    ..e. enzyme activation, nucleic acid stabilization, muscle contraction, secretion, or synaptic transmission)...
  11. IN VIVO CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS
    MARIA D DELIVORIA PAPADOPOULOS; Fiscal Year: 2010
    ..tyrosine phosphorylation at the active site of Src kinase (Tyr416) and EGFR kinase (Tyr1173), an index of enzyme activation, using specific anti-Tyr416-p-Src kinase and anti-Tyr1173-p-EGFR kinase antibodies to demonstrate activation ..
  12. Acinar Biology and Pancreatic Disease
    Guy E Groblewski; Fiscal Year: 2011
    ..It is widely believed that premature digestive enzyme activation is caused by abnormal interactions of the secretory and lysosomal pathways in acini...
  13. Detection strategies:Aptamer-based target recognition to turn-on GOx signaling
    MEHNAAZ FATIMA ALI; Fiscal Year: 2013
    ..respectively), is that a target- binding event via an aptamer probe will result in the direct release of an enzyme activation trigger...
  14. MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALING
    Nikolai O Artemyev; Fiscal Year: 2013
    ..the Gat2-mediated stimulation of cGMP-phoshodiesterase 6 is less potent in comparison to the effector enzyme activation in rods...
  15. Capitalizing on NSAID enantiomer selectivity for cancer prevention and therapy(PQ
    Angela Wandinger-Ness; Fiscal Year: 2013
    ..with the GDP-bound forms of the GTPases as predicted by cheminformatics, leading to blockade of GTP binding, enzyme activation and downstream cellular responses...
  16. CD44/VARIANT CYTOSKELETON IN BREAST CANCER PROGRESSION
    LILLY YW BOURGUIGNON; Fiscal Year: 2010
    ..g. NHE1-related acidic pH enzyme activation, ankyrin/cortactin-actin binding and PI3 kinase/AKT-mediated biological activities) required for ECM ..
  17. Near-Infrared Fluorescence Nanoparticles for Targeted O*
    Chun Li; Fiscal Year: 2009
    ..derived from Kodak's platform technology, and to design and develop nanoparticles that use targeting, enzyme activation, or a combination of both features to achieve significant improvements in the sensitivity and specificity of ..
  18. MECHANISMS OF HER2 HETERODIMERIZATION
    Ron Bose; Fiscal Year: 2013
    ..We developed a reconstituted in vitro system to study the heterodimerization and enzyme activation of Her2...
  19. Acinar Biology and Pancreatic Disease
    Guy E Groblewski; Fiscal Year: 2013
    ..It is widely believed that premature digestive enzyme activation is caused by abnormal interactions of the secretory and lysosomal pathways in acini...
  20. The Role of AID in Contact Sensitivity
    PHILIP WILLIAM ASKENASE; Fiscal Year: 2010
    ..The activity of these cells is dependent on the enzyme activation-induced deaminase (AID), which is involved in a number of steps in the assembly of the B cell receptor gene...
  21. AREA: Synthesis and Evaluation of New Cathepsin B, D, and K Inhibitors
    Rose McConnell; Fiscal Year: 2009
    ..The students will learn gene cloning techniques, protein expression and isolation, and enzyme activation techniques...
  22. Mechanical Injury and Repair in the Intervertebral Disc
    James C Iatridis; Fiscal Year: 2013
    ..The chronic experiments will evaluate how changes in the message levels and enzyme activation/inhibition may lead to alterations in protein content and disc structure.
  23. Chymotrypsin C in pancreatitis
    Miklos Sahin-Toth; Fiscal Year: 2013
    ..the present grant proposal are to determine the role of chymotrypsin C (CTRC) in the regulation of digestive enzyme activation and degradation and to investigate the mechanism(s) by which CTRC mutants act as risk factors for chronic ..
  24. MODIFIERS OF CARCINOGENESIS--ENVIRONMENTAL PAH MIXTURES
    William Baird; Fiscal Year: 2005
    ..studies will help us to relate the effects of complex PAH mixtures on DNA binding, tumor initiation and enzyme activation in mouse skin to how these mixtures affect carcinogen activation in humans. 3...
  25. PHYSIOLOGIC PHOSPHOLIPASE A2 ACTIVATION IN NEUTROPHILS
    SUE BAULDRY; Fiscal Year: 2000
    ..will utilize PMN permeabilized with Staphylococcus aureus alpha-toxin where cPLA2 is maintained in situ and enzyme activation is induced by addition of calcium, guanine nucleotides, and stimulation with a physiologic agonist...
  26. ADVANCED EPR STUDIES OF B12 DEPENDENT ENZYMES
    GARY GERFEN; Fiscal Year: 2005
    ..This "enzyme activation" of the cobalt-carbon bond j is a requirement for adenosylcobalamin-dependent catalysis.
  27. MOLECULAR MECHANISM OF MATRIX PROTEIN PHOSPHORYLATION
    CHOU WU; Fiscal Year: 1993
    ..growth factor-beta through quantitation of MPP kinase and changes in kinetics at different time course of enzyme activation. Vitamin D and transforming growth factor-beta as extracellular signals will first be added to cell culture ..
  28. AGE-RELATED INHIBITION OF DNA SYNTHESIS INITIATION
    David Busbee; Fiscal Year: 1991
    ....
  29. SOLUBLE AND INSOLUBLE FIBER DIETS IN HYPERLIPIDEMIA
    David Jenkins; Fiscal Year: 1991
    ..of the study with ultracentrifugal flotation, gel electrophoresis, rocket electroimmunoassay, GLC, and enzyme activation analysis. Clotting factors will be measured by radioimmunoassay...
  30. BIOCHEMICAL STUDIES OF CA2+ CHANNELS IN HEART CELLS
    Terry Rogers; Fiscal Year: 1992
    ..The mechanism of action of protein kinase C will be examined by measuring the effects of enzyme activation on the phosphorylation state of proteins, including the Ca2+ channel, in intact cultured cardiac myocytes...
  31. ECM PROTEASES IN INFLAMMATION, FIBROSIS & TUMORIGENESIS
    Gregory Goldberg; Fiscal Year: 2000
    ..the function of the carboxyl-end hemopexin-like domain, will be a focus for understanding of mechanisms of enzyme activation and interaction with the specific inhibitor TIMP2...
  32. Regulation of Calcineurin
    Paul Stemmer; Fiscal Year: 2005
    ..2) To determine the role of the CN-A amino terminus in enzyme activation, CN-A/CN-B interaction and NFAT substrate binding...
  33. PATHWAYS OF SKELETAL MUSCLE GLUCOSE METABOLISM IN MAN
    Lawrence Mandarino; Fiscal Year: 1991
    ..differ from those of physiologic hyperinsulinemia by comparing pathways of muscle glucose metabolism and enzyme activation at identical rates of muscle glucose uptake achieved with various combinations of hyperglycemia and ..
  34. MMP1 & MMP9: Mechanism of Activation & Substrate Binding
    Gregory Goldberg; Fiscal Year: 2009
    ..Specific Aims 2 and 3 propose to start with the gelatinase model to define biochemical interactions of gelatinases with substrate and to examine how these can enable processive diffusion and enzyme activation.
  35. ANG II AND IGF-1 INTERACTION IN CARDIOVASCULAR TISSUE
    James Sowers; Fiscal Year: 2003
    ..e., NO synthase [NOS] gene expression and NOS enzyme activation) and cation transport (Na+, K+-ATPase gene expression and pump activity)...
  36. AUTOPROTEOLYSIS OF N-TERMINAL NUCLEOPHILE HYDROLASE
    Hwai Chen Guo; Fiscal Year: 2004
    ..The enzymatic activities and enzyme activation are central to much of physiology. Dr...
  37. ACTIVATION OF PROTEIN KINASE C
    Michael Glaser; Fiscal Year: 1999
    ..lipids, calcium, and the substrates of protein kinase C phosphorylation under conditions that lead to enzyme activation. If the components are concentrated or ordered in a domain, this would greatly increase the reaction rate...
  38. Activation of CTP:phosphocholine cytidyltransferase
    JON FRIESEN; Fiscal Year: 2002
    ..In a cell, translocation of CT from a soluble pool to the membrane surface results in enzyme activation. Prior work has established that CT from rat is modular and comprises several functional domains, including ..
  39. GORDON CONFERENCE--MATRIX METALLOPROTEINASES
    Constance Brinckerhoff; Fiscal Year: 1993
    ..achieve these goals we will focus on themes such as molecular genetics and gene regulation,biochemistry of enzyme activation and inhibition, and the roles of these enzymes in normal development and in a number of disease processes, e...
  40. Biocatalytic Nanocomposites to Prevent Formation of Dental Plaque
    Jonathan Dordick; Fiscal Year: 2007
    ..To elucidate the mechanism of enzyme activation and stabilization on nanoscale materials, such as singlewalled carbon nanotubes, carbon buckyball aggregates,..
  41. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    NEKEISHA SWEENEY; Fiscal Year: 2007
    ..Raraty et al (2000) proposed a similar exchange could trigger the premature digestive enzyme activation in the pancreas leading to acute pancreatitis. However, this approach has never been thoroughly examined...
  42. ESTROGEN EFFICACY IN SPINAL CORD INJURY
    Naren Banik; Fiscal Year: 2006
    ..intervention of secondary damage involving Ca2+ overload, free radicals, glutamate toxicity, and enzyme activation. Investigations into cell and fiber damage, tissue destruction, neuron protection, and maintenance of ..
  43. HIV Protease Activation and Viral Replication
    Julie Nelson; Fiscal Year: 2006
    ..However, the precise effect of protease dimerization and subsequent enzyme activation on particle assembly and infectivity is unclear...
  44. AROMATIC L-AMINO ACID DECARBOXYLASE MODULATION
    NORTON NEFF; Fiscal Year: 2003
    ..AAAD activity undergoes short- and long-term changes in vivo, and enzyme activation and induction are involved...
  45. Regulation of guanylyl cyclase
    Ferid Murad; Fiscal Year: 2005
    ..The goal of this proposal is to determine the molecular mechanism of enzyme activation by alisoteric effectors including development of approaches for NO-independent regulation of sGC, ..
  46. PRESYNAPTIC RECEPTORS ON EMBRYONIC SENSORY NEURONS
    Kathleen Dunlap; Fiscal Year: 2007
    ..excitable cells, initiating events as diverse as exocytosis, membrane excitability, cell motility, enzyme activation, and gene induction...
  47. Regulation of Map Kinase by Protein Motions
    Natalie G Ahn; Fiscal Year: 2010
    ..HX-MS) and other measurements reveal three situations in which enzyme perturbations involving (i) enzyme activation, (ii) allosteric communication between binding sites, and (iii) mutagenesis lead to localized changes in ..
  48. SINGLE-MOLECULE DYNAMICS OF TARGET BINDING BY CALMODULIN
    CAREY JOHNSON; Fiscal Year: 2003
    ..The proposed research will also measure the coupling between CaM-binding and enzyme activation in the PMCA, permitting a detailed investigation of this mechanism...
  49. INBORN ERRORS OF SPHINGOLIPID CATABOLISM
    Gregory Grabowski; Fiscal Year: 2004
    ..Systematic site-directed mutagenesis, chimeric saposins, fluorescence energy transfer and enzyme activation will be used to identify such essential residues and regions for saposin C or B...
  50. Estrogen-Induced Neuroprotective Mitochondrial Mechanism
    ROBERTA BRINTON; Fiscal Year: 2007
    ..extensively utilized: neuronal culture, fluorescent intracellular calcium imaging, biochemical analyses of enzyme activation, immunocytochemical protein labeling, Western blot, mitochondrial isolation and HPLC for polyamines...
  51. NEUTROPHIL ACTIVATION OF THE OXIDATIVE BURST
    Robert Clark; Fiscal Year: 2004
    ..and the homologous NOH-1, as well as define cofactors, substrates, structural requirements and mechanisms of enzyme activation, (2) determine the possible role of NOH-1 as an antimicrobial host defense system in colon epithelium and (3)..
  52. Targeted Enzymes for Prodrug Therapy
    David Krag; Fiscal Year: 2007
    ..specimens and not to normal tissues using a novel fluorometric substrate, and 4) Characterize targeted enzyme activation of cytotoxic prodrugs in vitro and in vivo in animal models...
  53. MODULATION OF CALMODULIN AND THE CALCIUM SIGNAL
    Ruth Altschuld; Fiscal Year: 2003
    ..CaM isoform (hCLP) and of mutant paramecium CaM's to determine which are responsible for their differential enzyme activation and altered Ca binding...
  54. RETINOID METABOLISM IN STELLATE CELLS
    WILLIAM BOSRON; Fiscal Year: 2001
    ..The enzyme activation will be measured in cells...
  55. CALCIUM DYNAMICS AND INTRACELLULAR SIGNALING
    David Friel; Fiscal Year: 1999
    ..The kinetics of enzyme activation and deactivation will be examined in cell populations following imposed changes in [Ca2+]i...
  56. CPLA2 MEDIATED CELL DEATH AND BC1-2 REGULATION
    Adam Sapirstein; Fiscal Year: 2001
    ..To determine if nuclear membrane disruption and enzyme activation are the mechanisms for cPLA2-mediated potentiation of H202- induced cell death in renal epithelia cells...
  57. CELL BIOLOGY APPROACH TO DIABETIC RETINOPATHY
    George King; Fiscal Year: 2001
    ..isoform which has been reported to increase extracellular matrix production, growth factor expression, and enzyme activation. We have designed a specific PKC beta isoform inhibitor (LY333531) that can prevent many of the vascular ..
  58. DEREGULATING CYCLIN DEPENDENT KINASE
    FREDERICK CROSS; Fiscal Year: 2000
    ..towards which significant progress has been made) will allow dissection of the roles of cyclins in simple enzyme activation as opposed to targeting of the enzyme to specific substrates...
  59. Mitotic Regulation of Ribosomal S6 Protein Kinases
    Omar Shah; Fiscal Year: 2004
    ..multi-site phosphorylation that serves both to disable an auto-inhibitory mechanism and to directly induce enzyme activation. Over-activity or amplification of S6 kinases has been reported in a number of cancers indicating that anti-..
  60. MAGNETIC RESONANCE CARDIAC C13FLUX AND METABOLIC RATE
    E Lewandowski; Fiscal Year: 2001
    ..accounts for delayed C13 enrichment kinetics in postischemic hearts, (3) Regulation of TCA cycle flux by enzyme activation and metabolite influx / efflux can be observed in intact hearts with C13 NMR; (4) Reductions in glutamate ..
  61. CYCLIC AMP AND PROTEIN KINASES IN CELL REGULATION
    Charles Rubin; Fiscal Year: 2002
    ..Potential roles for PKAII-AKAP complexes in enzyme activation, secretion, cytoskeletal organization and gene transcription will be studied...