protein serine threonine kinases

Summary

Summary: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

Top Publications

  1. ncbi Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
    A Brunet
    Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 96:857-68. 1999
  2. ncbi The phosphatidylinositol 3-Kinase AKT pathway in human cancer
    Igor Vivanco
    Department of Medicine and Molecular Biology Institute, UCLA School of Medicine, 11 935 Factor Building, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nat Rev Cancer 2:489-501. 2002
  3. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
  4. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
  5. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
  6. 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
  7. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
  8. 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
  9. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
  10. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002

Detail Information

Publications316 found, 100 shown here

  1. ncbi Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
    A Brunet
    Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 96:857-68. 1999
    ..Within the nucleus, FKHRL1 triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene...
  2. ncbi The phosphatidylinositol 3-Kinase AKT pathway in human cancer
    Igor Vivanco
    Department of Medicine and Molecular Biology Institute, UCLA School of Medicine, 11 935 Factor Building, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nat Rev Cancer 2:489-501. 2002
  3. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals...
  4. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
    ..Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways...
  5. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
    ....
  6. 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...
  7. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
    ..These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR pathway of protein synthesis, cell growth, and viability in response to cellular energy levels...
  8. 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...
  9. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
    ..These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress...
  10. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
  11. 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...
  12. pmc Human CtIP promotes DNA end resection
    Alessandro A Sartori
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 450:509-14. 2007
    ..These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination...
  13. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations...
  14. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
    ..Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism...
  15. ncbi TGF-beta signal transduction
    J Massague
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Biochem 67:753-91. 1998
    ..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders...
  16. ncbi DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nature 434:864-70. 2005
    ..Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression...
  17. ncbi DNA double-strand breaks: signaling, repair and the cancer connection
    K K Khanna
    The Queensland Institute of Medical Research, and Department of Pathology, University of Queensland, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia
    Nat Genet 27:247-54. 2001
    ..Moreover, we discuss how tumor suppressor proteins such as p53, ATM, Brca1 and Brca2 have been linked to such pathways, and how accumulating evidence is connecting deficiencies in cellular responses to DNA DSBs with tumorigenesis...
  18. ncbi The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP
    Jianbin Huang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Cell 122:421-34. 2005
    ..Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene...
  19. ncbi AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
    Barbara B Kahn
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 1:15-25. 2005
    ..Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes...
  20. ncbi Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
    Coro Paisan-Ruiz
    Unitat de Genetica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València CSIC, E46010 Valencia, Spain
    Neuron 44:595-600. 2004
    ..Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor...
  21. 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...
  22. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth...
  23. 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...
  24. ncbi Cellular survival: a play in three Akts
    S R Datta
    Division of Neuroscience, Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA
    Genes Dev 13:2905-27. 1999
  25. ncbi Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity
    M Karin
    Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction University of California, San Diego, La Jolla, California 92093 0636, USA
    Annu Rev Immunol 18:621-63. 2000
    ....
  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 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...
  28. ncbi Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
    S C Bodine
    Regeneron Pharmaceuticals, Inc 777 Old Saw Mill River Road, Tarrytown, New York 10591 6707, USA
    Nat Cell Biol 3:1014-9. 2001
    ....
  29. ncbi Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Martin F Lavin
    Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
    Nat Rev Mol Cell Biol 9:759-69. 2008
    ....
  30. ncbi Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
    V Stambolic
    Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Cell 95:29-39. 1998
    ..Our results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway...
  31. pmc New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
    L C Cantley
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:4240-5. 1999
    ..PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides...
  32. ncbi Signaling to NF-kappaB
    Matthew S Hayden
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 18:2195-224. 2004
    ..In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity...
  33. 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...
  34. 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...
  35. ncbi Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
    Eros Lazzerini Denchi
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 448:1068-71. 2007
    ..The results reveal how mammalian telomeres use multiple mechanisms to avoid DNA damage surveillance and provide an explanation for the induction of replicative senescence and genome instability by shortened telomeres...
  36. ncbi Rocks: multifunctional kinases in cell behaviour
    Kirsi Riento
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London W1W 7BS, UK
    Nat Rev Mol Cell Biol 4:446-56. 2003
    ..Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states...
  37. ncbi Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls
    R J Kaufman
    Department of Biological Chemistry and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109 0650 USA
    Genes Dev 13:1211-33. 1999
  38. pmc IRE1 signaling affects cell fate during the unfolded protein response
    Jonathan H Lin
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94158, USA
    Science 318:944-9. 2007
    ..Key findings from our studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa...
  39. 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...
  40. 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...
  41. 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...
  42. pmc Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
    Daniel G Healy
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Lancet Neurol 7:583-90. 2008
    ..LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2?..
  43. ncbi hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts
    Shian Wu
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 114:445-56. 2003
    ..A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals...
  44. pmc Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint
    Q Liu
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:1448-59. 2000
    ..Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1...
  45. ncbi Chk1 and Chk2 kinases in checkpoint control and cancer
    Jiri Bartek
    Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Cancer Cell 3:421-9. 2003
    ....
  46. ncbi Un ménage à quatre: the molecular biology of chromosome segregation in meiosis
    Mark Petronczki
    Research Institute of Molecular Pathology, Dr Bohrgasse 7, 1030 Vienna, Austria
    Cell 112:423-40. 2003
    ....
  47. ncbi The TOR pathway: a target for cancer therapy
    Mary Ann Bjornsti
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 4:335-48. 2004
  48. ncbi Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
    C Rommel
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA
    Nat Cell Biol 3:1009-13. 2001
    ..In contrast, in addition to demonstrating that calcineurin does not mediate IGF-1-induced hypertrophy, we show that IGF-1 unexpectedly acts via Akt to antagonize calcineurin signalling during myotube hypertrophy...
  49. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997
    ..Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically...
  50. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
    ..Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response...
  51. ncbi A system for stable expression of short interfering RNAs in mammalian cells
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
    Science 296:550-3. 2002
    ..Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types...
  52. ncbi ATM phosphorylates histone H2AX in response to DNA double-strand breaks
    S Burma
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Biol Chem 276:42462-7. 2001
    ..Our results clearly establish ATM as the major kinase involved in the phosphorylation of H2AX and suggest that ATM is one of the earliest kinases to be activated in the cellular response to double-strand breaks...
  53. ncbi Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    K Kimura
    Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630 01, Japan
    Science 273:245-8. 1996
    ..Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase...
  54. ncbi Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase
    S A Hawley
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, United Kingdom
    J Biol Chem 271:27879-87. 1996
    ..A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., and Hardie, D. G. (1995) J. Biol. Chem. 270, 27186-27191)...
  55. 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...
  56. ncbi VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo
    Elizabeth A Harrington
    Vertex Pharmaceuticals Europe Limited, 88 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK
    Nat Med 10:262-7. 2004
    ..Our data indicate that Aurora kinase inhibition provides a new approach for the treatment of multiple human malignancies...
  57. ncbi Enhanced phosphorylation of p53 by ATM in response to DNA damage
    S Banin
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
    Science 281:1674-7. 1998
    ..Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM...
  58. ncbi Cell death by mitotic catastrophe: a molecular definition
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, Villejuif F 94805, France
    Oncogene 23:2825-37. 2004
    ....
  59. 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...
  60. pmc The Arabidopsis CDPK-SnRK superfamily of protein kinases
    Estelle M Hrabak
    Department of Plant Biology and Program in Genetics, University of New Hampshire, 46 College Road, Durham 03824, USA
    Plant Physiol 132:666-80. 2003
    ..The PlantsP database provides a resource of continuously updated information on protein kinases from Arabidopsis and other plants...
  61. 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...
  62. 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...
  63. 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...
  64. ncbi Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
    Jörg Urban
    Department of Molecular Biology, University of Geneva, Geneva, CH 1211, Switzerland
    Mol Cell 26:663-74. 2007
    ..Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt...
  65. ncbi Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
    C E Canman
    The Johns Hopkins School of Medicine, Oncology Center, Baltimore, MD 21205, USA
    Science 281:1677-9. 1998
    ..These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo...
  66. ncbi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 416:375-85. 2008
    ..The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity...
  67. pmc Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint
    Tony S Byun
    Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA
    Genes Dev 19:1040-52. 2005
    ....
  68. ncbi Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2
    J Gyuris
    Department of Molecular Biology, Massachusetts General Hospital, Boston 02114
    Cell 75:791-803. 1993
    ..These experiments identify Cdi1 as a novel type of protein phosphatase that forms complexes with cyclin-dependent kinases...
  69. ncbi Emerging roles of pseudokinases
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Trends Cell Biol 16:443-52. 2006
    ..We also discuss the emerging functions of other pseudokinases, including HER3 (also called ErbB3), EphB6, CCK4 (also called PTK7), KSR, Trb3, GCN2, TRRAP, ILK and CASK...
  70. ncbi AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
    D Grahame Hardie
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Nat Rev Mol Cell Biol 8:774-85. 2007
    ..Surprisingly, recent results indicate that the AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells...
  71. pmc Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
    Andrew B West
    Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:16842-7. 2005
    ..These results suggest a gain-of-function mechanism for LRRK2-linked disease with a central role for kinase activity in the development of PD...
  72. 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...
  73. 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...
  74. ncbi The phosphoinositide 3-kinase pathway
    Lewis C Cantley
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115 5713, USA
    Science 296:1655-7. 2002
    ..The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention...
  75. ncbi Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2
    Thomas G Hofmann
    Division of Immunochemistry G0200 German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Nat Cell Biol 4:1-10. 2002
    ..Interference with HIPK2 expression by antisense oligonucleotides impairs UV-induced apoptosis. Our results imply that HIPK2 is a novel regulator of p53 effector functions involved in cell growth, proliferation and apoptosis...
  76. pmc Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    J Cell Biol 190:73-87. 2010
    ..They also shed light on the relationship between the error correction pathway and the spindle checkpoint and suggest that these processes are coregulated and are likely to share at least a subset of their catalytic machinery...
  77. ncbi Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis
    Gabriella D'Orazi
    Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy
    Nat Cell Biol 4:11-9. 2002
    ..These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis...
  78. ncbi Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice
    H Cho
    Department of Biology, University of Pennsylvania, Philadelphia 19104, USA
    J Biol Chem 276:38349-52. 2001
    ....
  79. 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...
  80. ncbi The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response
    C Sidrauski
    Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143 0448, USA
    Cell 90:1031-9. 1997
    ..The addition of purified tRNA ligase completes splicing; we therefore have reconstituted HAC1 mRNA splicing in vitro from purified components...
  81. ncbi PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?
    M A Lawlor
    MRC Protein Phosphorylation Unit, Department of Life Sciences, University of Dundee, UK
    J Cell Sci 114:2903-10. 2001
    ..There are, however, a number of pitfalls of methodologies currently employed to study PKB function, and therefore caution should be used in interpretation of such experiments...
  82. ncbi RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems
    Koichi Kobayashi
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 416:194-9. 2002
    ..Rip2 is therefore a signal transducer and integrator of signals for both the innate and adaptive immune systems...
  83. ncbi A time-dependent phase shift in the mammalian unfolded protein response
    Hiderou Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Dev Cell 4:265-71. 2003
    ....
  84. ncbi The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
    Seung Hoi Koo
    Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, California 92037 1002, USA
    Nature 437:1109-11. 2005
    ..Individuals with type 2 diabetes often exhibit fasting hyperglycaemia due to elevated gluconeogenesis; compounds that enhance TORC2 phosphorylation may offer therapeutic benefits in this setting...
  85. pmc IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
    Kyungho Lee
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Genes Dev 16:452-66. 2002
    ..Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR...
  86. pmc Genomewide association study for susceptibility genes contributing to familial Parkinson disease
    Nathan Pankratz
    Indiana University School of Medicine, Health Information and Translational Sciences Building, Indianapolis, IN 46202 3002, USA
    Hum Genet 124:593-605. 2009
    ..8 x 10(-6); additive model: p = 4.8 x 10(-5)). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility...
  87. ncbi Kinase activity of mutant LRRK2 mediates neuronal toxicity
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
    Nat Neurosci 9:1231-3. 2006
    ..These data elucidate the pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms of sporadic Parkinson disease and suggest therapeutic targets...
  88. pmc LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 405:307-17. 2007
    ..The results of the present study suggest that moesin, ezrin and radixin may be LRRK2 substrates, findings that have been exploited to develop the first robust quantitative assay to measure LRRK2 kinase activity...
  89. pmc R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice
    Youren Tong
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:14622-7. 2009
    ..Together, our data suggest that the R1441C mutation in LRRK2 impairs stimulated dopamine neurotransmission and D2 receptor function, which may represent pathogenic precursors preceding dopaminergic degeneration in PD brains...
  90. ncbi Localization of LRRK2 to membranous and vesicular structures in mammalian brain
    Saskia Biskup
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Ann Neurol 60:557-69. 2006
    ..The studies herein explore the localization of LRRK2 in the mammalian brain...
  91. ncbi Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
    Keisuke Ito
    Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Nature 431:997-1002. 2004
    ..These results show that the self-renewal capacity of HSCs depends on ATM-mediated inhibition of oxidative stress...
  92. ncbi Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity
    Andrew B West
    Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 16:223-32. 2007
    ..These results suggest a link between LRRK2 kinase activity and pathogenic mechanisms relating to neurodegeneration, further supporting a gain-of-function role for LRRK2 mutations...
  93. pmc The coordinate regulation of the p53 and mTOR pathways in cells
    Zhaohui Feng
    Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA
    Proc Natl Acad Sci U S A 102:8204-9. 2005
    ..Thus, p53 and mTOR signaling machineries can cross-talk and coordinately regulate cell growth, proliferation, and death...
  94. ncbi Pseudo-DNA damage response in senescent cells
    Tatyana V Pospelova
    Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia
    Cell Cycle 8:4112-8. 2009
    ..Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells...
  95. pmc Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins
    Mar Carmena
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, King s Buildings, Edinburgh, Scotland, UK
    Curr Opin Cell Biol 21:796-805. 2009
    ..This review will focus on how interacting proteins make this functional diversity possible by targeting the kinases to different subcellular locations and regulating their activity...
  96. ncbi Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension
    K B Lane
    Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Nat Genet 26:81-4. 2000
    ..Our data demonstrate the molecular basis of FPPH and underscore the importance in vivo of the TGF-beta signalling pathway in the maintenance of blood vessel integrity...
  97. ncbi Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators
    Hui Jiang
    Institute of Neuroscience, Shanghai Institutes of Biological Sciences, The Graduate School, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
    Cell 120:123-35. 2005
    ....
  98. ncbi Human hypertension caused by mutations in WNK kinases
    F H Wilson
    Howard Hughes Medical Institute Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06510 USA
    Science 293:1107-12. 2001
    ..WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs...
  99. pmc IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates
    Dan Han
    Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 2520, USA
    Cell 138:562-75. 2009
    ..We propose that divergent cell fates during ER stress hinge on a balance between IRE1alpha RNase outputs that can be tilted with kinase inhibitors to favor survival...
  100. ncbi Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1
    F Urano
    Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
    Science 287:664-6. 2000
    ..Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals...
  101. 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...

Research Grants75

  1. Prevention of neointimal thickening by Mst1
    Junichi Sadoshima; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  2. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..Collectively, these outcomes will positively impact public health by providing a scientific basis for generating sound recommendations relative to these important toxins and appropriate remedial actions should exposures occur. ..
  3. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2013
    ..Understanding how these proteins work together will help to design new therapeutic approaches and possibly drugs for treatment of different human diseases and breast cancer. ..
  4. The role of IKK beta in cardiomyocytes at baseline and following stress
    MATTHEW PETER COGGINS; Fiscal Year: 2013
    ..abstract_text> ..
  5. Regulation of myocardial growth and death by GSK-3
    Junichi Sadoshima; Fiscal Year: 2013
    ..The knowledge obtained from this investigation should be useful for the development of better treatment for heart failure, ischemic injury and stem cell therapy. ..
  6. ALTERED CARDIAC MYOCYTE SIGNALING IN DIABETIC MYOCARDIUM AND FUNCTIONAL SEQUELAE
    ANTHONY JUSTIN MUSLIN; Fiscal Year: 2010
    ..The analysis of the role of Akt2 in diabetic cardiomyopathy may lead to new therapies that may help to reduce the high mortality rate associated with diabetes. ..
  7. Genetic &Functional Analyses of Hypertension Susceptibility Genes
    YEN PEI CHRISTY CHANG; Fiscal Year: 2013
    ..To accomplish these goals, we have brought together investigators who are experts in hypertension genetics, transcriptional regulation, bioinformatics, molecular biology, biochemistry, and renal physiology. ..
  8. The function of ATM protein in the biology of the adult neuron CNS:
    Karl Herrup; Fiscal Year: 2013
    ..The exploration of these phenomena will thus have significant value for our basic biological understanding of brain function as well as its malfunction in a number of different clinically relevant situations. ..
  9. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    ..These studies will also provide rationale for pharmacologic replacement or mimicry of LKB1 function in cancer prevention and treatment. ..
  10. Studying a novel regulator of GBM tumorigeneis: the role of CK2alpha in maintaini
    Gordon Li; Fiscal Year: 2013
    ..abstract_text> ..
  11. The Role of CD5 in B-Cell Development and Autoimmunity
    Chander Raman; Fiscal Year: 2012
    ..The role of CD5 in the development of B-cells has been extensively interrogated, but remains unresolved;the goal of this proposal is to fill this gap in our understanding. ..
  12. ATM Controls Genomic Stability in Pluripotent Stem Cells
    JASON MARK BECKTA; Fiscal Year: 2013
    ..The goal of this proposal is to contribute to a greater understanding of processes that will impact future treatments and augment our understanding of cellular biochemistry. ..
  13. Chromosomal Control of Segregation of C. Elegans
    Abby F Dernburg; Fiscal Year: 2013
    ..Through these approaches, we will learn how this molecular machine assembles from its component parts to govern the reassortment of genetic traits during sexual reproduction. ..
  14. Global Regulation of Gene expression in Streptococcus pneumoniae
    Bernard Weisblum; Fiscal Year: 2010
    ..pneumoniae, (2) To examine how these proteins regulate expression of the Piu heme transporter, and (3) To identify other genes regulated by the RitR/Stp/Stk complex. ..
  15. SFRP2 and NFAT are therapeutic targets in angiosarcoma
    NANCY K DEMORE; Fiscal Year: 2013
    ..Successful completion of the project will lead to clinical trials of these agents in patients with angiosarcoma in future studies. ..
  16. Tpl2 in Carcinogenesis-Related Inflammation
    KATHLEEN LEIGH DECICCO-SKINNER; Fiscal Year: 2011
    ..This proposal investigates the role of one such gene, Tpl2, and how its absence contributes to skin cancer development ..
  17. Peripheral T Cell tolerance by targeting AKT
    Claudio Anasetti; Fiscal Year: 2010
    ..The proposed studies will definitely evaluate the efficacy and mechanisms of TCN in controlling GVHD in clinically relevant models of BMT, and may point to a novel and more selective strategy to prevent GVHD in the clinic. ..
  18. GSK3beta, a mediator of ethanol neurotoxicity
    Xianglin Shi; Fiscal Year: 2013
    ..The current study is to determine whether C3G ameliorates ethanol-induced neuronal loss as well as behavioral deficits. The proposal will potentially develop a new therapeutic strategy. ..
  19. PCAF/GCN5 ACETYLATION ON P53 TRANSACTIVATION
    Shelley L Berger; Fiscal Year: 2013
    ..The proposed studies will advance our understanding of how p53 protects cells, and our results will raise the likelihood for pharmacologic regulation of p53 function to fight human cancer. ..
  20. TPL2: A Central Node in Obesity-Associated Inflammation and Metabolic Disorders
    Andrew S Greenberg; Fiscal Year: 2010
    ..Understanding the role of TPL2 in obesity may lead to potential new therapies for the complications of obesity such as diabetes. ..
  21. Targeting Mitotic Kinases Inhibitors for Cancer Therapy
    E Premkumar Reddy; Fiscal Year: 2013
    ....
  22. Sodium Chloride Cotransporter Regulation by WNK Kinase
    Hui Cai; Fiscal Year: 2010
    ....
  23. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2009
    ..abstract_text> ..
  24. Bone Morphogenic Protein Signaling Pathways in Uterine Biology
    Martin M Matzuk; Fiscal Year: 2013
    ....
  25. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2013
    ....
  26. Novel mechanisms of immune activation following allogeneic, hematopoietic stem ce
    JOHN JAMES LETTERIO; Fiscal Year: 2013
    ....
  27. SGK Regulation of Epithelial Sodium Transport
    David Pearce; Fiscal Year: 2013
    ..C) Examine the role of mTOR in regulation of amiloride-inhibitable currents in isolated CCD using patch clamp. ..
  28. Molecular genetics of epithelium formation in C. elegans
    Stephen E Von Stetina; Fiscal Year: 2010
    ..Positive candidates will be analyzed in detail to discover their role in establishing polarity. These results will add to our knowledge of this basic cell biological process and may identify therapeutic targets for human disease. ..
  29. Plk1-Numb Cooperation in Melanomagenesis
    Nihal Ahmad; Fiscal Year: 2013
    ..Our proposed study may lead to identification of novel strategies for the management of this deadly neoplasm. ..
  30. Inhibition of GRK2 to Prevent Ventricular Remodeling and Heart Failure After CABG
    Shahab A Akhter; Fiscal Year: 2013
    ..Inhibition of GRK2 activity has important therapeutic promise in this disease process and may represent a novel adjunctive therapy at the time of CABG. ..
  31. Polycomb-mediated epigenetic mechanisms in neurodegeneration and aging brain
    Hiroko Yano; Fiscal Year: 2013
    ..The pathways identified will aid in the development of novel therapeutics, which may potentially retard aging and slow neurodegeneration. ..
  32. Forms of HCV NS5A in vivo
    Craig E Cameron; Fiscal Year: 2013
    ..These studies have the ability to discover forms of HCV non-structural proteins unique to the infected hepatocyte and to reveal correlations between the level of these new forms and clinical outcomes. ..
  33. REGULATION OF MYOCARDIAL GROWTH AND DEATH BY THE HIPPO PATHWAY
    Junichi Sadoshima; Fiscal Year: 2013
    ..The knowledge obtained from these experiments should be useful for developing specific strategies to limit myocardial injury in patients with ischemic heart disease. ..
  34. Control of embryonic development by CK2: CK2 as a core Wnt/beta-catenin component
    María Isabel Domínguez; Fiscal Year: 2013
    ....
  35. Blood-based detection of BRAF DNA as a biomarker in metastatic melanoma patients
    David Polsky; Fiscal Year: 2012
    ....
  36. Structural Targeting Testis Specific Kinases (TSSK) 1 &2 for Male Contraception
    John C Herr; Fiscal Year: 2013
    ....
  37. Drak2-A Potential Therapeutic Target for Type 1 Diabetes
    Blaine Creasy; Fiscal Year: 2010
    ..These experiments will not only contribute to designing improved treatments for disease, but they will also elucidate the underlying cause of autoimmunity and perhaps uncover a novel mechanism of T cell regulation. ..
  38. MOLECULAR BASIS OF MAMMALIAN SPERM MOTILITY
    Jerome F Strauss; Fiscal Year: 2010
    ..The latter hypothesis is supported by the discovery of oligospermic males heterozygous for mutations that would affect PF20s expression. ..
  39. Protein Kinase C and GSTP1 interactions in glioma drug resistance
    Francis Ali-Osman; Fiscal Year: 2012
    ..The results are likely to lead to novel therapeutic strategies for malignant gliomas, particularly;those characterized by high GSTP1 expression and elevated or highly activated PKCs. ..
  40. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  41. Phosphorylation of PTH1R by TGF-betaRII in Bone Remodeling
    Tao Qiu; Fiscal Year: 2013
    ..This proposal may reveal a previously unrecognized function for T2RII in bone remodeling and a mechanism for PTH to regulate local growth factor at the level of membrane receptor. ..
  42. GPCR Kinase-2 in TNFalpha Signaling in Macrophages
    Narayanan Parameswaran; Fiscal Year: 2013
    ..Taken together, our studies should provide important insight into the mechanisms of TNF signaling in macrophages as well as identify potential therapeutic targets in the treatment of chronic inflammatory diseases. ..
  43. PI-3 kinase effectors in insulin-responsive systems
    Silvia Corvera; Fiscal Year: 2010
    ..4) Define the mechanism of action of WDFY2 by identifying proteins that specifically interact with its WD-40 motifs using proteomic and 2-hybrid approaches. ..
  44. THE CDK5/P35 KINASE
    Li Huei Tsai; Fiscal Year: 2013
    ....
  45. Characterization of WNK function in Axonal Maintenance
    Erin L Filbert; Fiscal Year: 2012
    ....
  46. A kinase pathway required for cortical neuron polarization
    Franck Polleux; Fiscal Year: 2012
    ..Therefore our work will provide important and novel clues regarding the molecular mechanisms underlying this devastating neurodegenerative pathology. ..
  47. Multimeric Signaling Complexes in PRLr Transduction
    Charles V Clevenger; Fiscal Year: 2013
    ..Third, the in vivo biologic relevance of the Nek3/Vav2 complex will be addressed through the study of Nek3-/- mice and breast cancer cell xenografts with altered levels of Nek3 activity. ..
  48. Regulation of Renal Maxi K Channel by WNK Kinase
    Hui Cai; Fiscal Year: 2013
    ....
  49. Chemical Genomic Approaches to Neurobiology of DISC1
    Li Huei Tsai; Fiscal Year: 2013
    ....
  50. ATM and DNA Damage in the Nervous System
    Peter J McKinnon; Fiscal Year: 2013
    ....
  51. B-RAF Regulation of the Cell Cycle in Melanoma
    Andrew E Aplin; Fiscal Year: 2013
    ..At the completion of our experiments, we aim to have identified new targets for therapeutic intervention to prevent aberrant melanoma cell proliferation. ..
  52. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID W CLAPP; Fiscal Year: 2012
    ..If the hypothesis is correct, we would predict that developing small molecules that inhibit Pak1 function could be useful as a molecular therapy for treatment of plexiform neurofibromas. ..
  53. STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONS
    Gary L Firestone; Fiscal Year: 2011
    ..A final goal is to functionally characterize the roles of GSK3 and CAS and their degradative systems in the steroid dependent control of beta-catenin dynamics, apical junction organization and tight junction formation. ..
  54. A Small Molecule to Activate Tumor Immunity after PLX403 in V600E BRAF Melanoma
    Barry Jones; Fiscal Year: 2013
    ..If ARI-4175 meets the test of feasibility in STTR Phase I, IND-enabling studies and initiation of clinical trials to investigae safety and efficacy will be proposed for Phase II. ..
  55. Therapeutic Role for P21 in Suppressing IL-1 Beta Mediated Pathologies
    HARRIS R PERLMAN; Fiscal Year: 2013
    ..These data indicate that p21 may be an inhibitor of arthritis and other inflammatory diseases. Therefore, our goal with these studies is to uncover the mechanism for p21-mediated inhibition of inflammation. ..
  56. RhoB in cancer pathogenesis and as a target in combinatorial therapy
    ROBERT SMALLRIDGE; Fiscal Year: 2013
    ..Our data indicate RhoB as a novel molecular switch dictating cell fate. Thusly, proposed studies have potential not only to improve understanding of RhoB signaling, but to ultimately lead to improved therapeutic approaches in ATC. ..
  57. GSK3 regulation of suprachiasmatic neuronal excitability and light entrainment
    JODI RENEE PAUL; Fiscal Year: 2013
    ....
  58. Isoform-specific function of y-AMPK in the heart.
    Rong Tian; Fiscal Year: 2013
    ....
  59. DAPK1 regulation of NMDA receptors in ischemic neuronal death
    NICOLAS GUILLERMO BAZAN; Fiscal Year: 2012
    ..Thus, this approach should not affect the physiological actions of glutamate receptors in the brain, thereby defining a promising target for stroke therapy. ..
  60. High-throughput assay development for molecular probes targeting the ULK1 kinase
    DEREK RONALD DUCKETT; Fiscal Year: 2013
    ....
  61. Regulation of autophagy by AMPK, Hsp90-Cdc37 and Ulk1 in erythroid cells
    Mondira Kundu; Fiscal Year: 2013
    ....
  62. High Throughput Screening to Discover Chemical Probes of ASK1
    LOUIS DANIEL SCAMPAVIA; Fiscal Year: 2013
    ....
  63. Biochemical Characterization of Yersinia Effector YopJ
    Kim Orth; Fiscal Year: 2012
    ..The three Specific Aims proposed for the renewal of this grant are designed to use genetics and biochemistry to study this novel inhibitory mechanism and to investigate its possible use in eukaryotic signaling pathways. ..
  64. ACTIONS OF CYCLIC GMP IN SMOOTH MUSCLE
    Thomas Lincoln; Fiscal Year: 1999
    ....
  65. DiosMemTM, a natural gamma-secretase inhibitor, opposes AD pathogenesis
    Jun Tan; Fiscal Year: 2009
    ..These studies will lay the foundation for AD clinical trials with DiosMemTM in the near future. ..
  66. ANTIGENIC DETERMINANTS OF VARICELLA VIRUS
    Charles Grose; Fiscal Year: 2006
    ..These proposed VZV studies will provide further insight into the multiple functions of gE and the gE:gI complex. ..
  67. REGULATION OF PLASMA CELL MALIGNANCY BY INSULIN AND IGF
    GREGORY FREUND; Fiscal Year: 2000
    ..Freund has a unique opportunity to develop into an outstanding clinician and scientist. ..
  68. Structure and mechanism of the AMP-activated protein kinase
    Lawrence Shapiro; Fiscal Year: 2010
    ..Our preliminary results and the further work proposed will provide high-resolution structural information on AMPK, and should directly enable the rational design of AMPK-directed therapeutics. ..
  69. PHOSPHORYLATION IN RENAL CELL INJURY
    Goutam Ghosh Choudhury; Fiscal Year: 2004
    ..These studies will identify important signaling mechanisms involved in glomerular pathology and help to establish effective therapeutic modalities for treatment of proliferative forms of GN. ..
  70. MOLECULAR BIOLOGY OF BRAIN PROTEIN PHOSPHORYLATION
    James Sikela; Fiscal Year: 1993
    ....
  71. REGULATION OF MIS TYPE II RECEPTOR AND TARGET GENES
    Jose Teixeira; Fiscal Year: 2002
    ....
  72. LTP AND SPATIAL LEARNING
    TIMOTHY TEYLER; Fiscal Year: 2002
    ..The drugs will also be given in combination. ..
  73. Molecular genetic analysis of UNC-82 kinase function in C. elegans muscle
    Pamela E Hoppe; Fiscal Year: 2010
    ..The human homologs of UNC-82 are expressed in heart and skeletal muscle. Understanding the role of UNC-82 in C. elegans will shed light on the role of the human enzymes in normal muscle development and function. ..
  74. SCHISTOSOME RECEPTOR SERINE/THRENONINE KINASE
    Edward Pearce; Fiscal Year: 1999
    ..Studies of the type proposed herein have the potential to provide a rational approach for developing appropriate therapeutics or prophylaxis (immuno-of-chemo-) for interrupting schistosome infection. ..
  75. Role of the Human Cytomegalovirus UL97 Proein Kinase in Viral Replication
    JEREMY KAMIL; Fiscal Year: 2009
    ..S. population, this research also offers to contribute to a better understanding of an important therapeutic drug target. ..