phosphorylation

Summary

Summary: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Top Publications

  1. 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
  2. pmc AKT/PKB signaling: navigating downstream
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, SPH2 117, Boston, MA 02115, USA
    Cell 129:1261-74. 2007
  3. pmc Human Protein Reference Database--2009 update
    T S Keshava Prasad
    Institute of Bioinformatics, International Tech Park, Bangalore 560 066, India
    Nucleic Acids Res 37:D767-72. 2009
  4. ncbi Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC
    P J Morin
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 275:1787-90. 1997
  5. ncbi Translating the histone code
    T Jenuwein
    Research Institute of Molecular Pathology IMP at the Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Science 293:1074-80. 2001
  6. ncbi A central role for JNK in obesity and insulin resistance
    Jiro Hirosumi
    Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
    Nature 420:333-6. 2002
  7. pmc The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation
    Vidisha Tripathi
    Department of Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Mol Cell 39:925-38. 2010
  8. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
  9. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
  10. 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

Detail Information

Publications348 found, 100 shown here

  1. 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...
  2. pmc AKT/PKB signaling: navigating downstream
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, SPH2 117, Boston, MA 02115, USA
    Cell 129:1261-74. 2007
    ..In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration...
  3. pmc Human Protein Reference Database--2009 update
    T S Keshava Prasad
    Institute of Bioinformatics, International Tech Park, Bangalore 560 066, India
    Nucleic Acids Res 37:D767-72. 2009
    ..include PhosphoMotif Finder, which allows users to find the presence of over 320 experimentally verified phosphorylation motifs in proteins of interest...
  4. ncbi Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC
    P J Morin
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 275:1787-90. 1997
    ..APC genes were found to contain activating mutations of beta-catenin that altered functionally significant phosphorylation sites...
  5. ncbi Translating the histone code
    T Jenuwein
    Research Institute of Molecular Pathology IMP at the Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Science 293:1074-80. 2001
    ....
  6. ncbi A central role for JNK in obesity and insulin resistance
    Jiro Hirosumi
    Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
    Nature 420:333-6. 2002
    ..Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics...
  7. pmc The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation
    Vidisha Tripathi
    Department of Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Mol Cell 39:925-38. 2010
    ..The serine/arginine (SR) splicing factors regulate tissue- or cell-type-specific AS in a concentration- and phosphorylation-dependent manner...
  8. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
    ..As expected, the C124S mutant of PTEN was incapable of catalyzing dephosphorylation of PtdIns(3,4,5)P3 consistent with the mechanism observed in protein-tyrosine phosphatase-catalyzed reactions...
  9. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
    ..the number introduced by each gray into the 6 x 10(9) base pairs of a mammalian G1 genome, leads to the gamma-phosphorylation of H2AX distributed over 1% of the chromatin. Thus, about 0...
  10. 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
    ..Akt/PKB activation requires the phosphorylation of Thr308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser473 within the ..
  11. pmc PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse
    Peter V Hornbeck
    Cell Signaling Technology, 3 Trask Lane, Danvers, MA 01923, USA
    Nucleic Acids Res 40:D261-70. 2012
    ..It encompasses 1,30,000 non-redundant modification sites, primarily phosphorylation, ubiquitinylation and acetylation. The interface is designed for clarity and ease of navigation...
  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 An integrated stress response regulates amino acid metabolism and resistance to oxidative stress
    Heather P Harding
    Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 11:619-33. 2003
    ..A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid ..
  14. 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
    ..in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins...
  15. 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
  16. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    ..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice...
  17. pmc An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1
    Carson C Thoreen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 284:8023-32. 2009
    ..These effects are at least partly mediated by mTORC1-dependent and rapamycin-resistant phosphorylation of 4E-BP1...
  18. 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
    ..We recently showed that insulin or insulin-like growth factor 1 induce the phosphorylation of PKB at two residues, Thr308 and Ser473...
  19. ncbi The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
    J W Harper
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030
    Cell 75:805-16. 1993
    ..p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes...
  20. 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...
  21. ncbi Mechanisms of type-I- and type-II-interferon-mediated signalling
    Leonidas C Platanias
    Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School, 710 North Fairbanks Court, Olson 8250, Chicago, Illinois 60611, USA
    Nat Rev Immunol 5:375-86. 2005
    ..It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance our current thinking about how interferons work...
  22. 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
    ..of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis...
  23. ncbi Focal adhesion kinase: in command and control of cell motility
    Satyajit K Mitra
    The Scripps Research Institute, Department of Immunology, IMM21 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 6:56-68. 2005
    ..Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement...
  24. doi Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis
    Jesper V Olsen
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D 82152 Martinsried near Munich, Germany
    Sci Signal 3:ra3. 2010
    ..and phosphoproteome of the human cell cycle on a global scale and quantified 6027 proteins and 20,443 unique phosphorylation sites and their dynamics...
  25. ncbi SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
    Estela Jacinto
    Department of Physiology and Biophysics, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cell 127:125-37. 2006
    ..Recent biochemical studies suggested that TORC2 is the elusive PDK2 for Akt/PKB Ser473 phosphorylation in the hydrophobic motif...
  26. pmc Megabase chromatin domains involved in DNA double-strand breaks in vivo
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Cell Biol 146:905-16. 1999
    ..from DNA double-strand breaks introduced into mammalian cells by ionizing radiation results in the specific phosphorylation of histone H2AX on serine residue 139, yielding a specific modified form named gamma-H2AX...
  27. pmc AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
    Joungmok Kim
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92130, USA
    Nat Cell Biol 13:132-41. 2011
    ..Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777...
  28. ncbi Stats: transcriptional control and biological impact
    David E Levy
    Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 3:651-62. 2002
    ..In addition to several roles in normal cell decisions, dysregulation of STAT function contributes to human disease, making the study of these proteins an important topic of current research...
  29. ncbi SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7
    Gareth J Inman
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London, UK
    Mol Pharmacol 62:65-74. 2002
    ..SB-431542 has no effect on components of the ERK, JNK, or p38 MAP kinase pathways or on components of the signaling pathways activated in response to serum...
  30. pmc Principles of interleukin (IL)-6-type cytokine signalling and its regulation
    Peter C Heinrich
    Institut fur Biochemie, RWTH Aachen, Universitatsklinikum, Pauwelsstrasse 30, D 52074 Aachen, Germany
    Biochem J 374:1-20. 2003
    ..Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed...
  31. 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...
  32. ncbi Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
    David A Guertin
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02141, USA
    Dev Cell 11:859-71. 2006
    ..but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKCalpha, but not S6K1...
  33. pmc GSK-3: tricks of the trade for a multi-tasking kinase
    Bradley W Doble
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Cell Sci 116:1175-86. 2003
    ..which has provided insight into GSK-3's penchant for primed substrates and the regulation of GSK-3 by serine phosphorylation, and findings related to the involvement of GSK-3 in the Wnt/beta-catenin and Hedgehog pathways...
  34. 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...
  35. ncbi Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
    Anne Brunet
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Center for Blood Research CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Science 303:2011-5. 2004
    ..Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance...
  36. ncbi A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
    T T Paull
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Curr Biol 10:886-95. 2000
    ..Recently it has been reported that a member of the histone H2A family, H2AX, becomes extensively phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites...
  37. 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
    ..TSC2 is inactivated by Akt-dependent phosphorylation, which destabilizes TSC2 and disrupts its interaction with TSC1...
  38. pmc A global protein kinase and phosphatase interaction network in yeast
    Ashton Breitkreutz
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada
    Science 328:1043-6. 2010
    ..An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses...
  39. 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...
  40. pmc Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth
    Philipp Wild
    Frankfurt Institute for Molecular Life Sciences and Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt Main, Germany
    Science 333:228-33. 2011
    ..In this work, we found that phosphorylation of an autophagy receptor, optineurin, promoted selective autophagy of ubiquitin-coated cytosolic Salmonella ..
  41. 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...
  42. 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...
  43. 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
    ..Exposure of cells to a variety of extracellular stimuli leads to the rapid phosphorylation, ubiquitination, and ultimately proteolytic degradation of IkappaB, which frees NF-kappaB to translocate to ..
  44. pmc Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Science 313:1137-40. 2006
    ..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes...
  45. 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
    ..Although shear-stress-mediated phosphorylation of eNOS is thought to regulate enzyme activity, the mechanism of activation of eNOS is not yet known...
  46. pmc Tau suppression in a neurodegenerative mouse model improves memory function
    K SantaCruz
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Science 309:476-81. 2005
    ..Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy...
  47. 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...
  48. ncbi STATs and gene regulation
    J E Darnell
    Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021, USA
    Science 277:1630-5. 1997
    ..Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA ..
  49. pmc AMPK phosphorylation of raptor mediates a metabolic checkpoint
    Dana M Gwinn
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Mol Cell 30:214-26. 2008
    ..AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain ..
  50. pmc AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha
    Sibylle Jäger
    Dana Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:12017-22. 2007
    ..These data indicate that AMPK phosphorylation of PGC-1alpha initiates many of the important gene regulatory functions of AMPK in skeletal muscle.
  51. ncbi A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress
    Michael Boyce
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 307:935-9. 2005
    ..More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events...
  52. pmc Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication
    Keril J Blight
    Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    J Virol 76:13001-14. 2002
    ....
  53. pmc Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization
    J A Diehl
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105 USA
    Genes Dev 12:3499-511. 1998
    ..b>Phosphorylation of cyclin D1 on a single threonine residue near the carboxyl terminus (Thr-286) positively regulates ..
  54. ncbi MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Science 316:1039-43. 2007
    ..Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well...
  55. ncbi Two-component signal transduction
    A M Stock
    Center for Advanced Biotechnology and Medicine and Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Annu Rev Biochem 69:183-215. 2000
    ..b>Phosphorylation induces a conformational change in the regulatory domain that results in activation of an associated domain ..
  56. 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
    ..Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive...
  57. pmc ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery
    Chang Hwa Jung
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
    Mol Biol Cell 20:1992-2003. 2009
    ..The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 inhibits autophagosome formation...
  58. ncbi Upstream and downstream of mTOR
    Nissim Hay
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
    Genes Dev 18:1926-45. 2004
    ..We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity...
  59. ncbi Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
    D D Sarbassov
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Biol 14:1296-302. 2004
    ..We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling ..
  60. pmc Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation
    Young Sik Cho
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell 137:1112-23. 2009
    ..RIP3 regulates necrosis-specific RIP1 phosphorylation. The phosphorylation of RIP1 and RIP3 stabilizes their association within the pronecrotic complex, activates ..
  61. doi Targeting the dynamic HSP90 complex in cancer
    Jane Trepel
    Medical Oncology Branch Center for Cancer Research, National Cancer Institute, Building 10, Room 1 5940, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Nat Rev Cancer 10:537-49. 2010
    ....
  62. pmc Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K
    Jessie Villanueva
    The Wistar Institute, Philadelphia, PA 19104, USA
    Cancer Cell 18:683-95. 2010
    ..Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF-1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors...
  63. ncbi Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
    Science 306:457-61. 2004
    ..of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptor substrate-1 (IRS-1)...
  64. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
    ..The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner...
  65. ncbi A probability-based approach for high-throughput protein phosphorylation analysis and site localization
    Sean A Beausoleil
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, Massachusetts 02115, USA
    Nat Biotechnol 24:1285-92. 2006
    ..and interpretation remain major logistical challenges when attempting to identify large numbers of protein phosphorylation sites by nanoscale reverse-phase liquid chromatography/tandem mass spectrometry (LC-MS/MS) (Supplementary ..
  66. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb...
  67. ncbi Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Manuela Neumann
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 314:130-3. 2006
    ..TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders...
  68. pmc Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy
    Daniel F Egan
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 331:456-61. 2011
    ..of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation...
  69. pmc Phospho.ELM: a database of phosphorylation sites--update 2011
    Holger Dinkel
    SCB Unit, EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
    Nucleic Acids Res 39:D261-7. 2011
    ..ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomic analyses...
  70. pmc A tissue-specific atlas of mouse protein phosphorylation and expression
    Edward L Huttlin
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 143:1174-89. 2010
    ..unique physiology requires tightly regulated gene and protein expression coordinated by specialized, phosphorylation-dependent intracellular signaling...
  71. 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
    ....
  72. ncbi Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB
    Dos D Sarbassov
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Mol Cell 22:159-68. 2006
    ..Our work describes an unforeseen mechanism of action for rapamycin that suggests it can be used to inhibit Akt/PKB in certain cell types...
  73. 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
    ..The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA...
  74. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  75. pmc PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
    Chandana Kondapalli
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Open Biol 2:120080. 2012
    ..We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser(65)...
  76. 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
    ..GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-..
  77. pmc Elucidation of a universal size-control mechanism in Drosophila and mammals
    Jixin Dong
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 130:1120-33. 2007
    ..Here we demonstrate that a single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway...
  78. pmc RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
    Poulikos I Poulikakos
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 464:427-30. 2010
    ..In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS...
  79. doi The role of adherens junctions and VE-cadherin in the control of vascular permeability
    Elisabetta Dejana
    FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Italy
    J Cell Sci 121:2115-22. 2008
    ..For instance, several factors, including vascular endothelial growth factor (VEGF), induce the tyrosine phosphorylation of VE-cadherin, which accompanies an increase in vascular permeability and leukocyte diapedesis; in addition, ..
  80. pmc The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries
    Moritz Treeck
    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell Host Microbe 10:410-9. 2011
    ..Protein phosphorylation is one mechanism by which these parasites can control such processes...
  81. pmc Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy
    Nao Hosokawa
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 20:1981-91. 2009
    ..ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex...
  82. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
    ..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
  83. ncbi Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism
    Chunming Liu
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Cell 108:837-47. 2002
    ..beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor ..
  84. 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...
  85. pmc Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration
    Ming Jin
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:5819-24. 2011
    ..We conclude that natural dimers isolated from the AD brain are sufficient to potently induce AD-type tau phosphorylation and then neuritic dystrophy, but passive immunotherapy mitigates this.
  86. 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
    ..activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation...
  87. ncbi Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions
    G Pearson
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Endocr Rev 22:153-83. 2001
    ..This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2...
  88. pmc PHOSIDA (phosphorylation site database): management, structural and evolutionary investigation, and prediction of phosphosites
    Florian Gnad
    Department for Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz, D 82152 Martinsried, Germany
    Genome Biol 8:R250. 2007
    PHOSIDA http://www.phosida.com, a phosphorylation site database, integrates thousands of high-confidence in vivo phosphosites identified by mass spectrometry-based proteomics in various species...
  89. 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
    ..The gene products of TSC1 and TSC2 form a functional complex and inhibit the phosphorylation of S6K and 4EBP1, two key regulators of translation...
  90. 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
    ..of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced by UV treatment...
  91. 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...
  92. pmc Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells
    Krishna M Vattem
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Proc Natl Acad Sci U S A 101:11269-74. 2004
    During cellular stresses, phosphorylation of eukaryotic initiation factor-2 (eIF2) elicits gene expression designed to ameliorate the underlying cellular disturbance...
  93. doi Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy
    Yoshinobu Ichimura
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Mol Cell 51:618-31. 2013
    ..However, the interplay between these two pathways remains largely unknown. Here, we show that phosphorylation of the autophagy-adaptor protein p62 markedly increases p62's binding affinity for Keap1, an adaptor of the ..
  94. pmc Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
    Bin Zhao
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 21:2747-61. 2007
    ..b>Phosphorylation by the Lats tumor suppressor kinase leads to cytoplasmic translocation and inactivation of the YAP ..
  95. pmc MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer
    Fanyin Meng
    Department of Internal Medicine, Scott and White Clinic, Texas A and M University System Health Science Center College of Medicine, Temple, Texas, USA
    Gastroenterology 133:647-58. 2007
    ..Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNA to tumor biology has not been established...
  96. pmc Phosphorylation of a WRKY transcription factor by two pathogen-responsive MAPKs drives phytoalexin biosynthesis in Arabidopsis
    Guohong Mao
    Department of Biochemistry, Interdisciplinary Plant Group, and Bond Life Sciences Center, University of Missouri, Columbia, Missouri 65211, USA
    Plant Cell 23:1639-53. 2011
    ..Furthermore, WRKY33 is a substrate of MPK3/MPK6. Mutation of MPK3/MPK6 phosphorylation sites in WRKY33 compromises its ability to complement the camalexin induction in the wrky33 mutant...
  97. pmc The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling
    Peggy P Hsu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 332:1317-22. 2011
    ..We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, ..
  98. pmc PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy
    Kahori Shiba-Fukushima
    Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113 8421, Japan
    Sci Rep 2:1002. 2012
    ..The introduction of mutations at Ser65 suggests that phosphorylation of Ser65 is required not only for the efficient translocation of Parkin, but also for the degradation of ..
  99. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
    ..mammalian signaling pathway homologous to the well studied yeast general control response in which eIF2alpha phosphorylation activates genes involved in amino acid biosynthesis...
  100. pmc A quantitative atlas of mitotic phosphorylation
    Noah Dephoure
    Department of Cell Biology, Harvard University Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:10762-7. 2008
    ..Protein phosphorylation by cyclin-dependent kinases (CDKs) drives this cycle...
  101. 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
    ....

Research Grants66

  1. Genetic variation and regulatory networks: Mechanisms and complexity
    DANA PE ER; Fiscal Year: 2009
    ..These tools will be made publicly available, including a friendly graphical user interface and visualization. ..
  2. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  3. Optimization of DNA Repair by Abh8
    Lauren Endres; Fiscal Year: 2013
    ..Based on predicative software analysis (ExPASy), there are a number of conserved phosphorylation and kinase recognition sites in human and mouse Abh8. Several of these kinases act in DDR signaling (i.e...
  4. Pyruvate Dehydrogenase kinase as Therapeutic Target for Hepatic Steatosis, Obesit
    Robert A Harris; Fiscal Year: 2012
    ..The activity of the pyruvate dehydrogenase complex (PDC) is tightly regulated by phosphorylation by the PDKs. The phosphorylation state of PDC is controlled by changes in expression level of the PDKs...
  5. MECHANISMS IN THE REGULATION OF SP-A GENE EXPRESSION
    Carole R Mendelson; Fiscal Year: 2013
    ..effects of O2 and inhibitory effects of glucocorticoids on SP-A expression are associated with changes in phosphorylation, DNA-binding and transcriptional activity of TTF-1 and NF-(B...
  6. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..by OPN-R in comparison to OPN-FL and OPN-L in terms of cell adhesion, cell proliferation, apoptosis, protein phosphorylation, gene expression and cytokine production...
  7. Phosphorylation of FGF23 coordinates crosstalk between the skeleton and kidney
    VINCENT SCOTT TAGLIABRACCI; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Research: Protein phosphorylation by protein kinases is an important regulatory mechanism that influences every aspect of cellular life...
  8. Angiotensin Adrenergic Interactions in the Kidney
    Roland C Blantz; Fiscal Year: 2013
    ..were overexpressed in the untreated A/I kidney including NADPH oxidase, heme-oxygenase-1 (HO-1),, and ERK 1/2 phosphorylation and functional nitric oxide activity was decreased...
  9. Ang II and Aldosterone Effects on Insulin Resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..several Ser kinases, including ROK, may inhibit insulin metabolic signaling by inducing site specific Ser phosphorylation of the critical docking protein insulin receptor substrate-1 (IRS-1)...
  10. Antiphospholipid antibodies and lupus: new molecular targets for treatment
    Emilio B Gonzalez; Fiscal Year: 2013
    ..affect aPL-mediated upregulation of TF, ICAM-1, cytokines and p38 mitogen activated protein kinase (p38 MAPK) phosphorylation in EC and activation of monocytes and platelets...
  11. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    ..In this proposal we are testing several novel hypotheses, 1) UBC9 protein half-life is affected by phosphorylation so that phosphorylation at critical site(s) protects against degradation, 2) SAMe and its metabolite ..
  12. Pathogenesis and Treatment of Liver Disease in Transaldolase Deficiency
    Andras Perl; Fiscal Year: 2013
    ..Reduced 2-catenin phosphorylation and enhanced c-jun expression in TAL-/- livers reflected adaptation to oxidative stress...
  13. Discovery of Small Molecule MBT Domain Antagonists
    STEPHEN VERNON FRYE; Fiscal Year: 2010
    ..acetylation;DNA cytosine methylation;and histone sumoylation, ubiquitination, ADP-ribosylation and phosphorylation.[2] Many of these modifications create a binding site to recruit other proteins which can 'read'..
  14. Role of Txnip in adapting fuel metabolism to nutritional state
    SIMON HUI; Fiscal Year: 2013
    ..Mitochondrial respiration will be measured by polarography and the defective component in the oxidative phosphorylation pathway will be identified...
  15. Right ventricular contractile dysfunction after pressure overload
    CLIFFORD RUSSELL GREYSON; Fiscal Year: 2013
    ..have proposed that calpain may be regulated by the non-voltage gated calcium channel TRPM7, by direct phosphorylation by the extracellular response kinase ERK, or by phosphorylation of calpain targets by the tyrosine kinase src...
  16. Cystathionine beta synthase (CBS) and angiogenesis
    Priyabrata Mukherjee; Fiscal Year: 2013
    ..VEGFR2 at the transcriptional and possibly at the translational level and downregulates ERK- 1/2 phosphorylation. Furthermore, silencing of CBS by siRNA leads to increased ROS production in HUVECs;c) Knockdown of CBS in ..
  17. Ang II and Overnutrition and Insulin resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..mTOR, a highly conserved nutrient sensor, modulates INS metabolic signaling through its phosphorylation (P) of S6K1, an evolutionarily conserved serine (Ser) kinase...
  18. Regulation of B Cell Function by Membrane-Cytoskeletal Remodeling
    Neetu Gupta; Fiscal Year: 2012
    ..Interestingly, BCR, but not SDF-11 stimulation induces robust phosphorylation of ezrin on unique tyrosine residues suggesting that ezrin participates in signal transduction downstream of ..
  19. Regulation of ER stress-induced cell death
    Randal J Kaufman; Fiscal Year: 2013
    ..A subpathway of the UPR is signaled through activation of the ER kinase PERK and phosphorylation of eukaryotic translation initiation factor 2 on the alpha subunit to transiently attenuate protein synthesis,..
  20. A Redox-active PARP Inhibitor for Lung Transplantation
    ANDREW LURIE SALZMAN; Fiscal Year: 2012
    ..Specific analyses will be carried out at 3 time points: at 1 h post reperfusion for I?B[unreadable], phosphorylation of MAP kinases, nuclear p50;at 3 h post reperfusion for RT-PCR to quantify lung mRNA concentrations of TNF-[..
  21. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..proline, alanine-rich kinase (SPAK) bind to WNK1 in cells, are WNK1 substrates, and are activated by WNK1 phosphorylation. The stimulus-dependent regulation of their association, specificity of their WNK binding, and the ion ..
  22. N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus Infecti
    Aquilur Rahman; Fiscal Year: 2010
    ..N-MCT is converted into the active triphosphate metabolite by a three step phosphorylation process, of which only the second step is selectively accomplished by HSV-TK...
  23. Patient-Derived Stem Cells for Phosphoproteomic Profiling Neuropsychopathology
    Dieter A Wolf; Fiscal Year: 2011
    ..Protein kinase pathways may be altered. Lithium alters MEK &ERK phosphorylation {Pardo, 2003 #162}, decreases CREB phosphorylation &activity of CaM kinase IV {Tardito, 2007 #163} in rat ..
  24. Med1 in Liver Metabolism, Regeneration and Cancer
    Janardan K Reddy; Fiscal Year: 2013
    ..determine how Med1-mediated functions of cell proliferation and metabolism are regulated by AMPK-mediated phosphorylation;and 3) characterize and use a transgenic mouse model in which Med1 can be expressed conditionally in ..
  25. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..in MYCN-amplified NB cells caused G1 cell cycle arrest and affected p27Kip1 levels, retinoblastoma protein Rb phosphorylation, and most intriguingly, blocked MYCN expression, thus providing a rationale for the potential use of ..
  26. MOLECULAR BASIS OF REOVIRUS PATHOGENESIS
    Terence S Dermody; Fiscal Year: 2013
    ..The phosphorylation status of JAM-A following reovirus attachment will be determined using wild-type and point-mutant JAM-A ..
  27. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2011
    ..These studies will determine the relative contribution of mTOR activation versus phosphorylation of FOXO1 and FOXO3 in suppressing cardiomyocyte autophagy...
  28. Mitochondrial Dysfunction and Adipose Insulin Resistance
    David A Bernlohr; Fiscal Year: 2013
    ..linkage between the antioxidant defense system in adipose cells with mitochondrial function, oxidative phosphorylation, signal transduction and the development of insulin resistance...
  29. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2013
    ..Two-dimensional peptide mapping identified three Tyr(s) of PAK1 which are phosphorylated by JAK2. Tyr phosphorylation of PAK1 by JAK2 was also shown to increase cell motility...
  30. Role and Regulation of INrf2
    ANIL KUMAR JAISWAL; Fiscal Year: 2013
    ..Mass spectra analysis of immunoprecipitated INrf2 from antioxidant untreated and treated cells demonstrated phosphorylation of specific serine, threonine and tyrosine residues that might control INrf2 functions but remains unknown...
  31. Inhibition of IkK to treat lethal Graft-vs.-Host Disease
    Patrick Flood; Fiscal Year: 2009
    ..is an inhibitor of the catalytic domain of IKK ? and blocks the activation of NF-?B by interfering with the phosphorylation of I?B. The founder of TheraLogics Al Baldwin PhD and the chief scientific officer Sankar Ghosh Ph.D...
  32. Role of Diabetes in Development of Renal Cell Carcinoma
    SAMY LEWIZ HABIB; Fiscal Year: 2013
    ..Certain agonists activate PI-3 kinase and Akt, which stimulate tuberin phosphorylation resulting in its inactivation...
  33. Neuroprotection and Myelin Repair Mechanisms in Multiple Sclerosis
    Inderjit Singh; Fiscal Year: 2013
    ..proliferator-activated receptor (PPAR) activity in various cell types and this was ascribed to direct PPAR phosphorylation or increased bio-availability of their endogenous activators...
  34. Molecular Regulation of Progesterone Synthesis
    John S Davis; Fiscal Year: 2013
    ..Two) To determine whether LH/PKA-dependent phosphorylation regulates the stability and activity of 2-catenin we will evaluate whether stimulation of PKA increases the ..
  35. MODULATION OF IFN ACTION VIA NOVEL REGULATORY FACTORS
    DHAN V KALVAKOLANU; Fiscal Year: 2013
    ..We hypothesize that ZIPK regulates DAPK1 expression by modulating the phosphorylation of C/EBP-binding domain of Med1. This aspect will be investigated in specific aim 3...
  36. Regulation of myocardial growth and death by GSK-3
    Junichi Sadoshima; Fiscal Year: 2013
    ..of cardiac hypertrophy and has substantial influence on cardiac function when its activity is modulated by phosphorylation during hypertrophy and heart failure (HF)...
  37. New insights in mechanisms of renal injury
    Balakuntalam S Kasinath; Fiscal Year: 2013
    ..In diabetic mice, renal cortical GSK 3beta is inactivated by Ser9 phosphorylation, and its substrate, the eukaryotic initiation factor 2B epsilon (eIF2Be), is activated...
  38. Regulation of AKAP79 Postsynaptic Membrane Targeting
    MARK L DELL'ACQUA; Fiscal Year: 2012
    ..b>Phosphorylation of AMPAR-GluR1 subunits by the cAMP-dependent protein kinase (PKA) may promote surface expression of AMPARs ..
  39. REGULATION OF PULMONARY CIRCULATION IN FETUS AND NEWBORN
    Girija G Konduri; Fiscal Year: 2013
    ..Increase in O2 availability and oxidative phosphorylation at birth may lead to increased reactive oxygen species (ROS) in mitochondria...
  40. A Thioredoxin Mimetic for Radiocontrast Nephropathy
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..Hyperactivation of PARP after CM injection depletes NAD stores, resulting in the loss of oxidative phosphorylation and interference with ATP synthesis...
  41. MOLECULAR MECHANISMS OF COMPLEX MIXTURE TOXICITY
    Alvaro Puga; Fiscal Year: 2013
    ..DNMT1 complexes to promoter chromatin and inhibiting phosphorylation, acetylation and methylation epigenetic marks established by BaP-induced gene transactivation in histones H3 ..
  42. Metabolic mechanisms of antiestrogen resistance in breast cancer
    UBALDO EMILIO MARTINEZ OUTSCHOORN; Fiscal Year: 2013
    ..We have recently demonstrated that a tumor stroma with increased reactive oxygen species (ROS), low oxidative phosphorylation metabolism (OXPHOS) and high glycolysis is found in aggressive breast cancers...
  43. TARGETING THE MARCKS-FAMILY PROTEINS TO INHIBIT NEUTROPHIL MIGRATION
    Mary K Sheats; Fiscal Year: 2013
    ..1 (MARCKSL1), are known cell membrane and actin binding proteins regulated by protein kinase C (PKC) phosphorylation and calcium/calmodulin binding...
  44. Hybrid Katp Channel Opener and Redox Catalyst for Lung Transplantation
    Prakash Jagtap; Fiscal Year: 2013
    ..analyses will be carried out at 3 time points: at 1 h post reperfusion for IkB[unreadable], nuclear p50, and phosphorylation of mitogen activated protein kinases (MAPKs - ERK, p38, JNK);at 3h post reperfusion for RT-PCR to quantify ..
  45. Regulation of Type 1 Interferon Production by Autoimmunity-Associated PTPN22
    Yaya Wang; Fiscal Year: 2013
    ..I will compare gene expression and transcription factor activation as well as IFN-dependent phosphorylation of STAT1 and upregulation of costimulatory molecules in wild-type and PTPN22 deficient cells after TLR ..
  46. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
    ..of oxidative stress and/or metabolomic analytes to activate inflammatory pathways in muscle leading to serine phosphorylation and desensitization of IRS and insulin signaling will be examined...
  47. PUFA Synthesis and the Control of Hepatic Metabolism
    Donald B Jump; Fiscal Year: 2013
    ..Elevated Elovl5 activity increased the phosphorylation and acetylation status of FoxO1 and attenuated the expression of genes involved in GNG, e.g...
  48. Sirtuin/FOXO Signaling in the Regulation of Bone Mass
    Stavroula Kousteni; Fiscal Year: 2012
    ..Treatment modalities aimed at restoring FOXO deacetylation and phosphorylation may form the basis for a novel approach to osteoporosis therapy. PUBLIC HEALTH RELEVANCE...
  49. Alzheimer's Disease Therapeutic
    Trevor P Castor; Fiscal Year: 2012
    ..in the brain and plasma compartments by total PKC activity, membrane/cytosolic PKC activity ratios, and phosphorylation of ERK 1/2 MAP Kinase;and (2) Specific Aim 2: Establish cGMP manufacturing of the bryostatin 1 API (active ..
  50. Cell signaling as a leukemia biomarker
    JAMES WILLIAM JACOBBERGER; Fiscal Year: 2013
    ..A significant component of cell signaling involves phosphorylation/de-phosphorylation cycles on pathway proteins, essentially from membrane surfaces to the genome, and between ..
  51. Ghrelin: Behavioral, Anatomical, and Physiological Components of Obesity
    BRETT JOHN WARREN TEUBNER; Fiscal Year: 2011
    ..a neurochemical measure of SNS drive) and from WAT, and two SNS-induced intracellular markers of lipolysis (phosphorylation of hormone sensitive lipase and perilipin A) by Western blot...
  52. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2012
    ..GSK3 inhibits glycogen synthase activity by phosphorylation of its serine/tyrosine residues...
  53. Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid Metabolism
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    ..that bile acid-mediated activation of S1P2 plays a critical role in regulating hepatic lipid metabolism by phosphorylation and activation of SphK2 in the nucleus...
  54. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford A Lowell; Fiscal Year: 2013
    ..b>Phosphorylation of these ITAM domains leads to recruitment of Syk/Zap70 kinases which in turn initiate downstream signaling, ..
  55. JNK exacerbates ischemia/reperfusion injury in hyperglycemic subjects.
    Keith A Webster; Fiscal Year: 2010
    ..fell by below 50%, a condition that sensitized myocytes to oxidative stress, and coincided with increased phosphorylation of the insulin receptor substrate-1 (IRS-1) on the inhibitory serine-307...
  56. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    ..that ligand occupancy of this site modulates post-translational modifications (acetylation, methylation, phosphorylation, etc.) of histones H3 or H4 that regulate gene transcription...
  57. BBP (Bone Morphogenetic Protein Binding Peptide) and Bone Healing
    SAMUEL SCOTT MURRAY; Fiscal Year: 2013
    ..of spp24 degradation on TGF-b signal transduction mediated by Smad-dependent pathways, assessed as R-Smad phosphorylation and nuclear translocation...
  58. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    ..We discovered a post-translational modification unique to K-Ras: protein kinase C (PKC) mediated phosphorylation. We found that phosphorylation of K-Ras at serine 181 partially neutralized the adjacent polybasic stretch of ..
  59. Interplay Between Tissue Architecture and Nuclear Organization in the DNA Damage
    Pierre Alexandre Vidi; Fiscal Year: 2013
    ..NuMA is rapidly phosphorylated upon DNA damage, is necessary for the maintenance of H2AX phosphorylation (a chromatin mark at DSBs), and interacts with the WICH chromatin remodeling complex that functions in the ..
  60. Nuclear-Cytoplasmic Shuttling of Foxc2 via 14-3-3 Determines Proximal Tubule Cell
    DIANA LYNNE GOLDEN; Fiscal Year: 2012
    ..My preliminary data suggests that phosphorylation at serine 125 shuttles Foxc2 out of the nucleus in proximal tubule cells...
  61. UV-induced and NOS-mediated Zn elevation, translation regulation and apoptosis
    Shiyong Wu; Fiscal Year: 2012
    ..Aim I, we proposed to elucidate the UV-induced and NO-mediated signaling pathway(s) that leads to eIF21 phosphorylation. The working hypothesis is that NO mediates UV-induced activations of eIF21 kinase(s), which phosphorylate ..
  62. Role of leptin-mediated PI3 Kinase signaling on reproductive control
    Carol Fuzeti Elias; Fiscal Year: 2013
    ..that the long isoform of LepRs mediates cell signaling via the JAK family of tyrosine kinases and subsequent phosphorylation of STAT3...
  63. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..linkage between the antioxidant defense system in adipose cells with mitochondrial function, oxidative phosphorylation, signal transduction and the development of insulin resistance...
  64. Using Mass Spectroscopy to Characterize Transcription Proteins and F2-Isoprostane
    BETTYE HENNINTON; Fiscal Year: 2011
    Project 1. Characterizing Phosphorylation Sites of Saccharomyces cerevisiae Transcription Factors, Rap1 and GcM Using Nanospray Mass Spectrometry Two Saccharomyces cerevisiae transcription factors, Raplp and Gcrlp, have been partially ..
  65. ANTIGENIC DETERMINANTS OF VARICELLA VIRUS
    Charles Grose; Fiscal Year: 2006
    ..For example, gE has endocytosis signals and both serine/threonine and tyrosine phosphorylation motifs in its cytoplasmic tail...
  66. REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
    Michael Garabedian; Fiscal Year: 2002
    The overall objectives of this proposal are to characterize the molecular mechanisms by which phosphorylation regulates glucocorticoid receptor (GR) activity...