serine

Summary

Summary: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES, PYRIMIDINES, and other amino acids.

Top Publications

  1. ncbi p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53
    K Oda
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
    Cell 102:849-62. 2000
  2. ncbi IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide
    Fan Yang
    Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA
    J Immunol 170:5630-5. 2003
  3. 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
  4. ncbi alpha-Synuclein is phosphorylated in synucleinopathy lesions
    Hideo Fujiwara
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Cell Biol 4:160-4. 2002
  5. ncbi Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease
    John P Anderson
    Elan Pharmaceuticals, South San Francisco, California 94080, USA
    J Biol Chem 281:29739-52. 2006
  6. doi Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
    Oliver D K Maddocks
    The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Nature 493:542-6. 2013
  7. 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
  8. pmc Phosphorylation of Serine 114 on Atg32 mediates mitophagy
    Yoshimasa Aoki
    Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812 8582, Japan
    Mol Biol Cell 22:3206-17. 2011
  9. pmc Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
    Richard Possemato
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 476:346-50. 2011
  10. pmc Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinase
    Hua Bai
    Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA
    Proc Natl Acad Sci U S A 108:7419-24. 2011

Detail Information

Publications405 found, 100 shown here

  1. ncbi p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53
    K Oda
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
    Cell 102:849-62. 2000
    ..Our results suggest that p53AIP1 is likely to play an important role in mediating p53-dependent apoptosis, and phosphorylation of Ser-46 regulates the transcriptional activation of this apoptosis-inducing gene...
  2. ncbi IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide
    Fan Yang
    Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA
    J Immunol 170:5630-5. 2003
    ..Here, we reported that LPS induced the phosphorylation of the p65 trans-activation domain on serine 536 in monocytes/macrophages...
  3. 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...
  4. ncbi alpha-Synuclein is phosphorylated in synucleinopathy lesions
    Hideo Fujiwara
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Cell Biol 4:160-4. 2002
    ..Furthermore, phosphorylation of alpha-synuclein at Ser 129 promoted fibril formation in vitro. These results highlight the importance of phosphorylation of filamentous proteins in the pathogenesis of neurodegenerative disorders...
  5. ncbi Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease
    John P Anderson
    Elan Pharmaceuticals, South San Francisco, California 94080, USA
    J Biol Chem 281:29739-52. 2006
    ....
  6. doi Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
    Oliver D K Maddocks
    The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Nature 493:542-6. 2013
    ..Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic ..
  7. 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 (..
  8. pmc Phosphorylation of Serine 114 on Atg32 mediates mitophagy
    Yoshimasa Aoki
    Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812 8582, Japan
    Mol Biol Cell 22:3206-17. 2011
    ..We also found that Hog1 and Pbs2, which are involved in the osmoregulatory signal transduction cascade, are related to Atg32 phosphorylation and mitophagy...
  9. pmc Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
    Richard Possemato
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 476:346-50. 2011
    ..PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux...
  10. pmc Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinase
    Hua Bai
    Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA
    Proc Natl Acad Sci U S A 108:7419-24. 2011
    Structural and topological data suggest that serine site-specific DNA recombinases exchange duplex DNAs by rigid-body relative rotation of the two halves of the synapse, mediated by a flat protein-protein interaction surface...
  11. pmc Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)
    Linda Vermeulen
    Department of Molecular Biology, University of Gent VIB, K L Ledeganckstraat 35, B 9000 Gent, Belgium
    EMBO J 22:1313-24. 2003
    ..This effect represents, together with phosphorylation of nucleosome components such as histone H3, an essential step leading to selective transcriptional activation of NF-kappaB-dependent gene expression...
  12. ncbi Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)
    J Zha
    Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 87:619-28. 1996
    ..In the presence of survival factor IL-3, cells phosphorylated BAD on two serine residues embedded in 14-3-3 consensus binding sites...
  13. ncbi Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at 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 275:9390-5. 2000
    ..The serine residue in this motif becomes rapidly phosphorylated in cells and animals when DNA double-stranded breaks are ..
  14. pmc TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal domain Ser7 residues, promoter-proximal pausing, and termination by RNA polymerase II
    Kira Glover-Cutter
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, UCHSC, MS 8101, P O Box 6511, Aurora, CO 80045, USA
    Mol Cell Biol 29:5455-64. 2009
    ..Consistent with a new role for TFIIH at 3' ends, it was detected within genes and 3'-flanking regions, and Cdk7 inhibition delayed pausing and transcription termination...
  15. pmc Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
    P M Tedeschi
    1 Department of Medicine, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA 2 Department of Pharmacology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
    Cell Death Dis 4:e877. 2013
    Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. We have predicted that a fraction of the synthesized serine is routed to a pathway for ATP production...
  16. ncbi Glia-derived D-serine controls NMDA receptor activity and synaptic memory
    Aude Panatier
    INSERM, U378, Bordeaux, F 33077, France
    Cell 125:775-84. 2006
    ..Its activation requires the binding of both glutamate and a co-agonist like D-serine to its glycine site...
  17. 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
    ..Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46...
  18. pmc Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue
    J Chen
    Howard Hughes Medical Institute, Department of Chemistry, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 92:4947-51. 1995
    ....
  19. pmc Serine, glycine and one-carbon units: cancer metabolism in full circle
    Jason W Locasale
    Field of Biochemistry and Molecular Cell Biology, Cornell University, Ithaca New York 14850, USA
    Nat Rev Cancer 13:572-83. 2013
    ..Given the wealth of clinically available agents that target one-carbon metabolism, these new findings could present opportunities for translation into precision cancer medicine. ..
  20. pmc Mechanism of activation of protein kinase B by insulin and IGF-1
    D R Alessi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    EMBO J 15:6541-51. 1996
    ..We propose a model whereby PKBalpha becomes phosphorylated and activated in insulin/IGF-1-stimulated cells by an upstream kinase(s)...
  21. ncbi Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing
    Seong Hoon Ahn
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 13:67-76. 2004
    ..This domain consists of a repeated heptameric sequence (YSPTSPS) phosphorylated at serines 2 and 5. Serine 5 is phosphorylated during initiation and recruits capping enzyme...
  22. ncbi Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    J Biol Chem 277:48115-21. 2002
    ..One mechanism mediating insulin resistance may involve the phosphorylation of serine residues in insulin receptor substrate-1 (IRS-1), leading to impairment in the ability of IRS-1 to activate ..
  23. doi Glial D-serine gates NMDA receptors at excitatory synapses in prefrontal cortex
    Pascal Fossat
    Institut National de la Santé et de la Recherche Médicale U862, Neurocentre Magendie, 33077 Bordeaux, France
    Cereb Cortex 22:595-606. 2012
    ..Their activation requires the binding of glutamate and also of a coagonist. Whereas glycine and D-serine (D-ser) are candidates for such a role at central synapses, the nature of the coagonist in cerebral cortex remains ..
  24. ncbi Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133
    G A Gonzalez
    Clayton Foundation Laboratory for Peptide Biology, Salk Institute, La Jolla, California 92037
    Cell 59:675-80. 1989
    ....
  25. pmc Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness
    Jun Hong
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cancer Res 71:3980-90. 2011
    ..However, the mechanisms responsible for regulating Twist1 stability are unknown in these cells. We identified the serine 68 (Ser 68) as a major phosphorylation site of Twist1 by mass spectrometry and with specific antibodies...
  26. doi Serine codon-usage bias in deep phylogenomics: pancrustacean relationships as a case study
    Omar Rota-Stabelli
    Department of Biology, The National University of Ireland, Maynooth, Co Kildare, Ireland
    Syst Biol 62:121-33. 2013
    ..and the amino acids-based trees is caused by substitutions within synonymous codon families (especially those of serine-TCN and AGY)...
  27. ncbi 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation
    S R Datta
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 6:41-51. 2000
    ..These findings define a mechanism by which survival signals inactivate a proapoptotic Bcl-2 family member, and suggest a role for 14-3-3 proteins as cofactors that regulate sequential protein phosphorylation events...
  28. ncbi Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function
    Frederic Luciano
    INSERM Unit 526, LNC Label, Faculte de Medecine, 28 Avenue de Valombrose, 06107 Nice Cedex 02, France
    Oncogene 22:6785-93. 2003
    ..Using different cellular models we evidence that serine 69 is both necessary and sufficient for Erk1/2-mediated phosphorylation and degradation of Bim-EL...
  29. ncbi IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain
    H Sakurai
    Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, 16 89 Kashima 3 chome, Yodogawa ku, Osaka 532 8505, Japan
    J Biol Chem 274:30353-6. 1999
    ..Furthermore, activation of IKKs by NF-kappaB-inducing kinase induced phosphorylation of p65 in vivo. Our finding, together with previous observations, suggests dual roles for IKK complex in the regulation of NF-kappaB.IkappaB complex...
  30. pmc Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization
    Nicolas Dzamko
    University of Dundee, Scotland, UK
    Biochem J 430:405-13. 2010
    ..Since a common mutation that replaces Gly2019 with a serine residue enhances kinase catalytic activity, small-molecule LRRK2 inhibitors might have utility in treating ..
  31. ncbi Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases
    Bing Hao
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 26:131-43. 2007
    ....
  32. ncbi Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance
    R A Campbell
    Department of Surgery, Indiana University School of Medicine, Indianapolis 46202, USA
    J Biol Chem 276:9817-24. 2001
    ..Taken together, these results define a molecular link between activation of the PI 3-kinase/AKT survival pathways, hormone-independent activation of ERalpha, and inhibition of tamoxifen-induced apoptotic regression...
  33. doi Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins
    Gen Matsumoto
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute and CREST JST, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Mol Cell 44:279-89. 2011
    ..Here, we show that the specific phosphorylation of p62 at serine 403 (S403) in its ubiquitin-associated (UBA) domain increases the affinity between UBA and polyubiquitin chain, ..
  34. pmc Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2
    Xianming Deng
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Nat Chem Biol 7:203-5. 2011
    ..LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson's disease...
  35. ncbi Alternative splicing of pre-mRNAs of Arabidopsis serine/arginine-rich proteins: regulation by hormones and stresses
    Saiprasad Goud Palusa
    Department of Biology, Colorado State University, Fort Collins, CO 80523, USA
    Plant J 49:1091-107. 2007
    ..Here, we show that the pre-mRNAs of Arabidopsis genes that encode serine/arginine-rich (SR) proteins, a conserved family of splicing regulators in eukaryotes, are extensively ..
  36. pmc Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine
    Jean Pierre Mothet
    Laboratoire de Neurobiologie Cellulaire et Moleculaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 9040, Institut Fédératif de Neurobiologie Alfred Fessard, F 91198 Gif sur Yvette, France
    Proc Natl Acad Sci U S A 102:5606-11. 2005
    The gliotransmitter D-serine is released upon (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate and metabotropic glutamate receptor stimulation, but the mechanisms involved are unknown...
  37. doi Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists
    Thomas Papouin
    INSERM U862, Neurocentre Magendie, 33077 Bordeaux, France
    Cell 150:633-46. 2012
    ..We report that synaptic and extrasynaptic NMDARs are gated by different endogenous coagonists, d-serine and glycine, respectively...
  38. ncbi Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NF-kappaB activity
    Holger Buss
    Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Biol Chem 279:49571-4. 2004
    ..Using a combination of peptide arrays with in vitro kinase assays we identify serine 468 as a novel phosphorylation site of p65 NF-kappaB...
  39. ncbi Diversity in the serine recombinases
    Margaret C M Smith
    Institute of Genetics, Queens Medical Centre, University of Nottingham, NG7 2UH, UK
    Mol Microbiol 44:299-307. 2002
    ..These are the tyrosine recombinases or lambda integrase family and the serine recombinases or resolvase/invertase family...
  40. pmc Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances
    Abigail Polter
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294 0017, USA
    Neuropsychopharmacology 35:1761-74. 2010
    ..mood stabilizers, antipsychotics, antidepressants, and mood-regulating neuromodulators increase the inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3), we hypothesized that deficient GSK3 serine-phosphorylation ..
  41. pmc Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint
    Chunying Yang
    Department of Radiation Oncology, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX 77030, USA
    Mol Cell 44:597-608. 2011
    ..that mitotic ATM activation is dependent on the Aurora-B kinase and that Aurora-B phosphorylates ATM on serine 1403. This phosphorylation event is required for mitotic ATM activation...
  42. ncbi Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway
    J Nakae
    Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:15982-5. 1999
    ..FKHR proteins contain potential sites for phosphorylation by the serine/threonine kinase Akt...
  43. pmc SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776
    Lisa Duvick
    Institute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
    Neuron 67:929-35. 2010
    ..Ser776 is critical for the pathway to neuronal dysfunction, while an expanded polyglutamine tract is essential for neuronal death...
  44. pmc Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex
    Bojan Drobic
    Department of Immunology, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Manitoba R3E 0V9, Canada
    Nucleic Acids Res 38:3196-208. 2010
    ..of the ERK and p38 MAPK pathways, the MSK1/2-mediated nucleosomal response, including H3 phosphorylation at serine 28 or 10, is coupled with the induction of immediate-early (IE) gene transcription...
  45. ncbi Phosphorylation of serine 10 in histone H3, what for?
    Claude Prigent
    Groupe Cycle Cellulaire, UMR 6061 Génétique et Développement, CNRS, 250 Université de Rennes I, IFR 97 Génomique Fonctionnelle et Santé, Faculte de Medecine, 2 Avenue du Pr Leon Bernard, CS 34317, 35043 Rennes Cedex, France
    J Cell Sci 116:3677-85. 2003
    ..What is the kinase and under what circumstances does Ser10 becomes phosphorylated? Most importantly, what are the consequences of phosphorylation of this residue?..
  46. doi Extensive coupling of alternative splicing of pre-mRNAs of serine/arginine (SR) genes with nonsense-mediated decay
    Saiprasad G Palusa
    Department of Biology, Program in Molecular Plant Biology, Program in Cell and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA
    New Phytol 185:83-9. 2010
    In Arabidopsis, pre-mRNAs encoding serine/arginine (SR) proteins, key regulators of constitutive and alternative splicing, are extensively alternatively spliced...
  47. pmc Serine is a natural ligand and allosteric activator of pyruvate kinase M2
    Barbara Chaneton
    Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK
    Nature 491:458-62. 2012
    ..enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine...
  48. pmc Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4
    Xiaohong Zhang
    H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    Genes Dev 19:827-39. 2005
    ..unlike other class I HDACs, HDAC3 uniquely copurifies with the catalytic and regulatory subunits of the protein serine/threonine phosphatase 4 complex (PP4c/PP4R1)...
  49. pmc A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability
    Pierre Olivier Esteve
    New England Biolabs, Ipswich, Massachusetts, USA
    Nat Struct Mol Biol 18:42-8. 2011
    ..In mammalian cells, phosphorylated DNMT1 is more stable than methylated DNMT1. These results reveal cross-talk on DNMT1, through modifications mediated by AKT1 and SET7, that affects cellular DNMT1 levels...
  50. pmc 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization
    R Jeremy Nichols
    University of Dundee, Scotland, UK
    Biochem J 430:393-404. 2010
    ..These results provide the first evidence suggesting that 14-3-3 regulates LRRK2 and that disruption of the interaction of LRRK2 with 14-3-3 may be linked to Parkinson's disease...
  51. pmc Structure-guided reprogramming of serine recombinase DNA sequence specificity
    Thomas Gaj
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:498-503. 2011
    ..Early studies on the directed evolution of serine recombinase DNA sequence specificity produced enzymes with relaxed substrate specificity as a result of randomly ..
  52. pmc Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu
    Andrey A Tokarev
    Department of Medicine University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0679, USA
    J Virol 85:51-63. 2011
    ..However, a serine-threonine-serine sequence specifically mediates the downregulation of BST-2 from the cell surface and the optimal ..
  53. doi Relationship between mutation of serine residue at 315th position in M. tuberculosis catalase-peroxidase enzyme and Isoniazid susceptibility: an in silico analysis
    Rituraj Purohit
    School of Bio Sciences and Technology, Bioinformatics Division, Vellore Institute of Technology University, Vellore, 632014 Tamil Nadu, India
    J Mol Model 17:869-77. 2011
    ..INH) is mediated by Mycobacterium tuberculosis catalase-peroxidase (MtBKatG) and mutation at position 315 (serine to threonine) leads to resistance...
  54. pmc Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2
    K D Copps
    Howard Hughes Medical Institute, Division of Endocrinology, Boston Children s Hospital, Harvard Medical School, CLS 16020, 300 Longwood Avenue, Boston, MA 02115, USA
    Diabetologia 55:2565-82. 2012
    ..However, IRS1 and IRS2 are regulated through a complex mechanism involving phosphorylation of >50 serine/threonine residues (S/T) within their long, unstructured tail regions...
  55. pmc Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission
    H Wolosker
    Departments of Neuroscience, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 96:13409-14. 1999
    ..Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate/N-methyl-D-aspartate receptors by interacting with ..
  56. ncbi The activity of leukocyte NADPH oxidase: regulation by p47PHOX cysteine and serine residues
    Bernard M Babior
    The Scripps Research Institute, La Jolla, CA 92037, USA
    Antioxid Redox Signal 4:35-8. 2002
    ..Its activity is also regulated, however, by the four cysteines of the same subunit, as indicated by the replacement of those cysteines by alanines...
  57. pmc Resolving discrepancy between nucleotides and amino acids in deep-level arthropod phylogenomics: differentiating serine codons in 21-amino-acid models
    Andreas Zwick
    Department of Entomology, State Museum of Natural History, Stuttgart, Germany
    PLoS ONE 7:e47450. 2012
    ..This study investigates the cause of that discrepancy...
  58. pmc A role for glycosylated serine-rich repeat proteins in gram-positive bacterial pathogenesis
    A Lizcano
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 3900, USA
    Mol Oral Microbiol 27:257-69. 2012
    ..b>Serine-rich repeat proteins (SRRPs) are a family of adhesins in Gram-positive bacteria that mediate attachment to a ..
  59. pmc Androgen receptor serine 81 phosphorylation mediates chromatin binding and transcriptional activation
    Shaoyong Chen
    Hematology Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 287:8571-83. 2012
    Our previous findings indicated that androgen receptor (AR) phosphorylation at serine 81 is stimulated by the mitotic cyclin-dependent kinase 1 (CDK1)...
  60. ncbi p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation
    Song Ja Kim
    Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500 712, Korea
    J Biol Chem 277:33501-8. 2002
    ..Activated p38 kinase also physically associates and phosphorylates the serine 15 residue of p53, which results in accumulation of p53 protein during NO-induced apoptosis...
  61. doi mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation
    Rachel L Yamnik
    Department of Biology, Stern College for Women of Yeshiva University, New York, NY 10016, USA
    FEBS Lett 584:124-8. 2010
    ..We report that the mTOR/S6K1 and MAPK/RSK contribute non-overlapping inputs into ERalpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors...
  62. pmc NMDA receptors regulate GABAA receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the γ2 subunit
    James Muir
    Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom
    Proc Natl Acad Sci U S A 107:16679-84. 2010
    ..Moreover, the dispersal of GABA(A)R clusters and increased mobility of individual GABA(A)Rs are dependent on serine 327 within the intracellular loop of the GABA(A)R γ2 subunit...
  63. pmc CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation
    Vicki Gordon
    University of Virginia, Department of Microbiology, Charlottesville, Virginia 22908, USA
    Mol Endocrinol 24:2267-80. 2010
    ..Phosphorylation is specific to S81 because CDK9 did not phosphorylate the AR on other serine phosphorylation sites...
  64. pmc STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation
    J Chung
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 17:6508-16. 1997
    Recent studies have indicated that serine phosphorylation regulates the activities of STAT1 and STAT3. However, the kinase(s) responsible and the role of serine phosphorylation in STAT function remain unresolved...
  65. ncbi Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo
    Ya Ling Hsu
    Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
    J Pharmacol Exp Ther 318:484-94. 2006
    ..Activation of JNK by plumbagin phosphorylated p53 at serine 15, resulting in increased stability of p53 by decreasing p53 and MDM2 interaction...
  66. ncbi Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia
    Kenji Hashimoto
    Department of Psychiatry, Graduate School of Medicine, Chiba University, Japan
    Arch Gen Psychiatry 60:572-6. 2003
    ..Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site of the NMDA receptor...
  67. pmc A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability
    I E Gallouzi
    Institut de Genetique Moleculaire de Montpellier, UMR 5535 CNRS, Universite Montpellier II, F34293 Montpellier Cedex 5, France
    Mol Cell Biol 18:3956-65. 1998
    ..In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity...
  68. ncbi Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein
    M Okochi
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 275:390-7. 2000
    ..Phosphoamino acid analysis revealed that phosphorylation occurred predominantly on serine. Using site-directed mutagenesis we have identified a major phosphorylation site at serine 129 within the C-..
  69. pmc mTORC2 protein complex-mediated Akt (Protein Kinase B) Serine 473 Phosphorylation is not required for Akt1 activity in human platelets [corrected]
    Samantha F Moore
    School of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom
    J Biol Chem 286:24553-60. 2011
    ..Together, these results demonstrate that mTORC2 is the kinase that phosphorylates Akt Ser(473) in human platelets but that this phosphorylation is dispensable for Thr(308) phosphorylation and Akt1 activity...
  70. ncbi Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity
    Louisa Varinou
    Max F Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Microbiology and Genetics, University of Vienna, Dr Bohr Gasse 9 4, A1030 Vienna, Austria
    Immunity 19:793-802. 2003
    Stat1 is phosphorylated on serine 727 within its transactivating domain (TAD) in response to interferons or other immunological signals. We generated gene-targeted mutant mice expressing a serine727-alanine mutant of Stat1...
  71. ncbi Phosphorylation of RelA/p65 on serine 536 defines an I{kappa}B{alpha}-independent NF-{kappa}B pathway
    Carl Y Sasaki
    Laboratory of Immunology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 280:34538-47. 2005
    ..In addition, serine phosphorylation at various sites of the p65 subunit has been shown to be important in initiating transcription...
  72. ncbi HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway
    Y Wen
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA
    Cancer Res 60:6841-5. 2000
    ..Akt specifically binds to AR and phosphorylates serines 213 and 791 of AR. Thus, Akt is a novel activator of AR required for HER-2/neu signaling to androgen-independent survival and growth of prostate cancer cells...
  73. doi Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori
    Nicole Tegtmeyer
    Department of Microbiology, Otto von Guericke University, Leipziger Strasse 44, D 39120 Magdeburg, Germany
    Cell Host Microbe 9:520-31. 2011
    ..pylori (Hp) targets cortactin by two independent processes leading to its tyrosine dephosphorylation and serine phosphorylation to regulate cell scattering and elongation...
  74. pmc Dcp2 phosphorylation by Ste20 modulates stress granule assembly and mRNA decay in Saccharomyces cerevisiae
    Je Hyun Yoon
    Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
    J Cell Biol 189:813-27. 2010
    ..We show that during stress in Saccharomyces cerevisiae, Dcp2 is phosphorylated on serine 137 by the Ste20 kinase...
  75. doi Glutamate receptor-like genes form Ca2+ channels in pollen tubes and are regulated by pistil D-serine
    Erwan Michard
    Instituto Gulbenkian de Ciencia, Rua da Quinta Grande, 6, P 2780 156 Oeiras, Portugal
    Science 332:434-7. 2011
    ..Additionally, wild-type pollen tubes grown in pistils of knock-out mutants for serine-racemase (SR1) displayed growth defects consistent with a decrease in GLR activity...
  76. pmc ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
    R Maya
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Genes Dev 15:1067-77. 2001
    ..Both putative 2A10 epitopes are highly conserved and encompass potential phosphorylation sites. Serine 395, residing within the carboxy-terminal 2A10 epitope, is the major target on Mdm2 for phosphorylation by ATM in ..
  77. pmc Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7
    Minkyu Kim
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 284:26421-6. 2009
    ..Within the repeating sequence YSPTSPS, serines 2 and 5 are major phosphorylation sites, but serine 7 phosphorylation was recently discovered in mammalian cells...
  78. ncbi Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin
    K Orford
    Lombardi Cancer Center, Georgetown University Medical Center, Washington, D C 20007, USA
    J Biol Chem 272:24735-8. 1997
    ..Mutation of a single serine within the ubiquitination targeting sequence prevents ubiquitination of beta-catenin...
  79. pmc Phosphorylation of eIF2α at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency
    Hala Muaddi
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, QC, H3T 1E2, Canada
    Mol Biol Cell 21:3220-31. 2010
    ..that converge on the phosphorylation of the alpha (α) subunit of eukaryotic translation initiation factor eIF2 at serine 51 (S51), a modification that results in a global inhibition of protein synthesis...
  80. ncbi Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding
    Xiaohui Zhang
    Department of Medicine, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 277:45276-84. 2002
    ..Binding is rapid and reversible, providing an opportunity for the phosphorylation of Ser-256 and subsequent phosphorylation of Thr-24 and Ser-319 and nuclear exclusion of FKHR...
  81. ncbi Functional interaction of yeast pre-mRNA 3' end processing factors with RNA polymerase II
    Donny D Licatalosi
    Department Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver 80262, USA
    Mol Cell 9:1101-11. 2002
    ..Consistent with this model, the 3' end processing factors CFIA, CFIB, and PFI were recruited to genes progressively, starting at the 5' end, in a process that required ongoing transcription...
  82. ncbi RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint
    Erin Olson
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, LA, Jolla, California 92037, USA
    J Biol Chem 281:39517-33. 2006
    ..Threonine 21 and serine 33, two residues among several phosphorylation sites in the amino terminus of RPA2, are specifically required for ..
  83. pmc Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites
    Sairei So
    Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    J Cell Biol 187:977-90. 2009
    ..In response to DNA double-strand breaks (DSBs), ATM is autophosphorylated at serine 1981...
  84. pmc Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation
    J A Brockman
    Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0295, USA
    Mol Cell Biol 15:2809-18. 1995
    ..Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive ..
  85. ncbi PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation
    Alessio Zippo
    Dipartimento di Biologia Molecolare Università di Siena, Via Fiorentina 1, 53100 Siena, Italy
    Nat Cell Biol 9:932-44. 2007
    The serine/threonine kinase human Pim1 (hereafter PIM1) cooperates with human c-Myc (hereafter MYC) in cell cycle progression and tumorigenesis. However, the nature of this cooperation is still unknown...
  86. ncbi Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14
    W S Lo
    Molecular Genetics Program, Wistar Institute, Philadelphia, Pennsylvania 19024, USA
    Mol Cell 5:917-26. 2000
    ..We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes ..
  87. ncbi Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase
    Yasunari Takada
    Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 278:24233-41. 2003
    ..Although H2O2 activated IkappaBalpha kinase, it did not induce the serine phosphorylation of IkappaBalpha...
  88. pmc Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission
    Magalie Martineau
    Neurocentre Magendie, National Institute of Health and Medical Research, Unit 862 and University of Bordeaux, F 33077 Bordeaux, France
    J Neurosci 33:3413-23. 2013
    ..astrocytes have been shown recently to release small molecules, such as the amino acids l-glutamate and d-serine as "gliotransmitters," which directly control the efficacy of adjacent synapses...
  89. doi L-serine synthesis in the central nervous system: a review on serine deficiency disorders
    L Tabatabaie
    Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht and Netherlands Metabolomics Centre, The Netherlands
    Mol Genet Metab 99:256-62. 2010
    The de novo synthesis of the amino acid L-serine plays an essential role in the development and functioning of the central nervous system (CNS)...
  90. pmc Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane of collecting duct principal cells
    Hanne B Moeller
    The Water and Salt Research Center, Institute of Anatomy, University of Aarhus, Aarhus, Denmark
    Kidney Int 75:295-303. 2009
    ..We recently identified a novel form of aquaporin-2 that is phosphorylated at serine-269 (pS269-AQP2)...
  91. pmc Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1
    Kevin Garofalo
    MGH Neuroscience Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 121:4735-45. 2011
    ..It is caused by several missense mutations in the genes encoding 2 of the 3 subunits of the enzyme serine palmitoyltransferase (SPT)...
  92. ncbi Bruton's tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NFkappaB activation by lipopolysaccharide
    Sarah L Doyle
    Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland
    J Biol Chem 280:23496-501. 2005
    ..Additionally LFM-A13 impaired phosphorylation of serine 536 on p65 induced by LPS in HEK293-TLR4 cells, and in Xid macrophages this response was impaired...
  93. pmc Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation
    Katrin Friedbichler
    Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
    Blood 116:1548-58. 2010
    ..To analyze the hitherto unrecognized role of Stat5 serine phosphorylation in this context, we have generated cS5 constructs with mutated C-terminal serines 725 and 779, ..
  94. pmc c-Jun N-terminal kinase enhances MST1-mediated pro-apoptotic signaling through phosphorylation at serine 82
    Wenzhi Bi
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
    J Biol Chem 285:6259-64. 2010
    ..The MST1 encodes a serine/threonine kinase that is activated upon apoptotic stimulation, which in turn phosphorylates its downstream targets,..
  95. doi Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is important for fanconi anemia pathway function and BRCA2 interaction
    Gang Zhi
    Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia, USA
    Cancer Res 69:8775-83. 2009
    ..In this study, we report a novel phosphorylation site serine 331 (S331) of FANCD2, the pivotal downstream player of the Fanconi anemia pathway...
  96. pmc Phosphorylation at serine 331 is required for Aurora B activation
    Eleni Petsalaki
    Department of Biology, University of Crete, Heraklion 71409, Greece
    J Cell Biol 195:449-66. 2011
    ..In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells...
  97. doi Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation
    Tomoko Kobayashi
    Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
    Hum Mutat 31:284-94. 2010
    ..in RAF1 were clustered in the conserved region 2 (CR2) domain, which carries an inhibitory phosphorylation site (serine at position 259; S259)...
  98. doi Human RBMY regulates germline-specific splicing events by modulating the function of the serine/arginine-rich proteins 9G8 and Tra2-{beta}
    Natacha Dreumont
    IGBMC Department of Functional Genomics, Illkirch, France
    J Cell Sci 123:40-50. 2010
    ..and transformer-2 protein homolog beta (Tra2-beta), mediated by multiple regions of the RBMY protein that contain serine/arginine-rich dipeptides, but not by the single region lacking such dipeptides...
  99. doi Calcineurin dephosphorylates glycogen synthase kinase-3 beta at serine-9 in neuroblast-derived cells
    Yeni Kim
    Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
    J Neurochem 111:344-54. 2009
    ..We conclude that in vitro, calcineurin can dephosphorylate GSK-3beta at Ser-9 and form a stable complex with GSK-3beta, suggesting the possibility that calcineurin regulates the dephosphorylation and activation of GSK-3betain vivo...
  100. ncbi Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1
    Hung Kai Chen
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 113:457-68. 2003
    ..Our finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention...
  101. pmc Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study
    Gabriel M Simon
    Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 285:11051-5. 2010
    ..protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.

Research Grants72

  1. REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
    Michael Garabedian; Fiscal Year: 2002
    ..Of these, the cyclin-dependent kinases (Cdks) phosphorylate serine 232 (S232) and serine (S224), while c-Jun N- terminal kinase (JNK) phosphorylates serine 246 (S246) and glycogen ..
  2. CARDIOPROTECTIVE AGENTS IN ISCHEMIC MYOCYTES
    RICHARD HONKANEN; Fiscal Year: 2002
    ..level, fostriecin is a potent inhibitor of type 2A, a strong inhibitor of type 5, and a weak inhibitor of type 1 serine/threonine protein phosphatases, suggesting that the cardioprotective properties of fostriecin arise from its ..
  3. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..and to provide 'proof of principal'for therapeutic intervention with a new class of anti-inflammatory serine protease inhibitor (serpin) therapeutics...
  4. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..showed that prochemerin, a novel chemoattractant whose activity is dependent on C-terminal proteolytic cleavage by serine protease(s), can be activated by sequential cleavages by plasmin and CPB, thus establishing a new substrate for ..
  5. Pharmacogenetics of obesity and endocannabinergic modulation (POEM)
    Russell A Wilke; Fiscal Year: 2012
    ..Degradation of AEA is catalyzed by a serine amidase, fatty acid amide hydrolase (gene name FAAH)...
  6. Multi-targeted Countermeasures against Acute and Delayed Effects of OP Exposure
    John A Butera; Fiscal Year: 2013
    ..the effects of excess acetylcholine, the oxime-based reactivator plays the key role of cleaving the phosphorylated serine esteratic site to release the active AChE molecule...
  7. Ang II and Aldosterone Effects on Insulin Resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..We posit that activation of serine (Ser) kinase signaling pathways, in conjunction with excess generation of reactive oxygen species (ROS), ..
  8. Cystathionine beta synthase (CBS) and angiogenesis
    Priyabrata Mukherjee; Fiscal Year: 2013
    ..dependent and the first rate-limiting enzyme in the transsulfuration pathway that catalyzes the condensation of L-serine and L-homocysteine (Hcy) to produce cystathionine, an intermediate step in the synthesis of cysteine (Cys)...
  9. Ang II and Overnutrition and Insulin resistance in Cardiovascular Tissue
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..sensor, modulates INS metabolic signaling through its phosphorylation (P) of S6K1, an evolutionarily conserved serine (Ser) kinase...
  10. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..The Ste20 protein kinase oxidative stress responsive 1 (OSR1) and its homolog the serine, proline, alanine-rich kinase (SPAK) bind to WNK1 in cells, are WNK1 substrates, and are activated by WNK1 ..
  11. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..of 18S and 28S ribosomal (r)RNA, 2) double-stranded RNA-activated protein kinase (PKR), a ribosome-associated serine-threonine kinase, is essential for DON-induced protein kinase activation and 3) DON induces mobilization of ..
  12. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2013
    ..Preliminary data demonstrate that the serine-threonine kinase PAK1 associates with and is Tyr phosphorylated by JAK2...
  13. Role and Regulation of INrf2
    ANIL KUMAR JAISWAL; Fiscal Year: 2013
    ..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...
  14. Hepcidin-based screening for infantile iron deficiency
    Mark D Fleming; Fiscal Year: 2010
    ..Recently, we identified biallelic mutations in the liver-specific transmembrane serine protease, TMPRSS6, in individuals with the phenotype opposite to hereditary hemochromatosis-a disorder termed iron ..
  15. The Kallikrein/Kinin-Mast Cell Interaction in Volume Overload
    CHIH CHANG KEVIN WEI; Fiscal Year: 2013
    ..effect, BK is chemotactic for inflammatory cells, in particular mast cells (MCs), which are the source of the serine protease chymase...
  16. The role of IKK beta in cardiomyocytes at baseline and following stress
    MATTHEW PETER COGGINS; Fiscal Year: 2013
    ..Understanding NF-kB's role in the heart thus has important practical implications. The serine-threonine kinase, Inhibitor of Kappa B Kinase beta (IKKB), is the primary activator of NF-kB in response to ..
  17. Regulation of myocardial growth and death by GSK-3
    Junichi Sadoshima; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, plays an important role in regulating growth and death of cardiomyocytes...
  18. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
    ..These latter compounds activate various serine kinases, such as PKC or IKK2 (in association with activation of NF-:B), which then phosphorylate insulin receptor ..
  19. ALTERED CARDIAC MYOCYTE SIGNALING IN DIABETIC MYOCARDIUM AND FUNCTIONAL SEQUELAE
    ANTHONY JUSTIN MUSLIN; Fiscal Year: 2010
    ..Insulin action is dependent on the activation of an intracellular signaling pathway that stimulates the serine/threonine kinase Akt2, leading to increased glucose uptake, glucose oxidation and glycogen synthesis...
  20. Molecular mechanisms of lung disease in ataxia telangiectasia
    JoAnn M Sekiguchi; Fiscal Year: 2013
    ..The gene mutated in A-T, ataxia-telangiectasia mutated (ATM), has been identified and encodes a large serine-threonine protein kinase...
  21. Identification and Analysis of Flavivirus Protease and RNA Helicase Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2009
    ..NS3, in association with NS2B, is a serine protease that is required for polyprotein processing, a key early event in the virus life cycle...
  22. Mechanisms of Endothelin 1-Induced Sickle Cell Pathology
    Alicia Rivera; Fiscal Year: 2011
    ..Moreover, we demonstrated that ET-1 regulates the activity of casein kinase II (CK2), a ubiquitous serine/threonine protein kinase found in eukaryotic cells that phosphorylate acidic proteins...
  23. Functional Analysis of the Dual Specificity Kinase NEK1 in Mammalian Meiosis
    JOANNA KIM HOLLOWAY; Fiscal Year: 2011
    ..NEK1 is a dual activity serine/threonine and tyrosine kinase, and is highly expressed in germ cells, particularly the narrow window encompassing ..
  24. 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...
  25. Ceramide Metabolism and Photoreceptor Homeostasis
    Usha R Acharya; Fiscal Year: 2013
    ..Mutations in serine palmitoyl transferase 1, the rate-limiting enzyme of the sphingolipid biosynthetic pathway leads to Hereditary ..
  26. JNK exacerbates ischemia/reperfusion injury in hyperglycemic subjects.
    Keith A Webster; Fiscal Year: 2010
    ..stress, and coincided with increased phosphorylation of the insulin receptor substrate-1 (IRS-1) on the inhibitory serine-307...
  27. Molecular Mechanisms of Disease Progression in Myeloid Malignancy
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..We identified GAS2 as another relevant Icsbp-target-gene. Gas2 inhibits calpain;a serine protease with substrates that include bcate-nin, Stat3, Stat5 and Xiap...
  28. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    ..We found that phosphorylation of K-Ras at serine 181 partially neutralized the adjacent polybasic stretch of amino acids and thereby activated a farnesyl-..
  29. 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...
  30. Interactions of the RAAS and a Western Diet on Insulin Metabolic Actions
    JAMES RUSSELL SOWERS; Fiscal Year: 2013
    ..sensor, modulates INS metabolic signaling through its phosphorylation [(p)] of S6K1, an evolutionarily conserved serine (Ser) kinase...
  31. Intracellular Serpin Regulation of Intestinal Cell Necrosis
    GARY ARTHUR SILVERMAN; Fiscal Year: 2012
    ..Since some of these intracellular serpins (serpinsIC) neutralize lysosomal cysteine and serine peptidases, we hypothesized that they regulate intracellular proteolysis and enhance cell survival...
  32. Genetic &Functional Analyses of Hypertension Susceptibility Genes
    YEN PEI CHRISTY CHANG; Fiscal Year: 2013
    ..Our prior GWAS effort demonstrated that variants in the serine-threonine kinase, STK39, are associated with BP and highlighted an incompletely understood network of kinases and ..
  33. The function of ATM protein in the biology of the adult neuron CNS:
    Karl Herrup; Fiscal Year: 2013
    ..In this location, it serves as a serine-threonine kinase but equally as a chaperone protein that nucleates a complex of proteins that includes vesicle ..
  34. 14th International Workshop on Ataxia-Telangiectasia and ATM
    Richard A Gatti; Fiscal Year: 2010
    ..ATM gene encodes a large (369 kDa) protein, ATM, which is a member of the phosphatidyl inositol 3 kinase family of serine/threonine protein kinases...
  35. The Effects of PP2A on TNF Signaling and Smoke-Induced Lung Injury
    Robert F Foronjy; Fiscal Year: 2013
    ..This is significant since PP2A is the primary serine threonine protein phosphatase present in all eukaryotic cells...
  36. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2011
    ..Mask phenotype was traced to a splicing error affecting the type II transmembrane serine protease 6 (TMPRSS6)...
  37. MECHANISMS OF GASTROINTESTINAL GROWTH AND TRANSFORMATION
    Juanita L Merchant; Fiscal Year: 2013
    ..Butyrate also triggers auto-phosphorylation of ATM at serine 1981 (pATMS1981) that subsequently complexes with ZBP-89 to activate p21...
  38. Vitamin B6 Effects on One-Carbon Metabolism
    Jesse F Gregory; Fiscal Year: 2013
    ..essential roles in the acquisition and processing of one-carbon (1C) units by the glycine cleavage system and serine hydroxymethyltransferase, inter conversion and catabolism of amino acids, control of homocysteine, and production ..
  39. KINETICS OF DRUG MACROMOLECULE COMPLEX FORMATION
    PALMER WILLIAM TAYLOR; Fiscal Year: 2013
    ..the oxyanion hole, the nucleophile rendering catalytic triad and the hydrogen bonding network between the proximal serine hydroxyls at the base of the gorge...
  40. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): (Also known as serine/threonine kinase 11, STK11) tumor suppressor is mutationally inactivated in Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder characterized by gastrointestinal polyps, ..
  41. Regulation of the Endothelial Citrulline-Nitric Oxide Cycle
    Duane C Eichler; Fiscal Year: 2010
    ..Based on our evidence that insulin regulates AS expression and serine-threonine phosphorylation, the first aim of this proposal is designed to explore the mechanisms by which insulin ..
  42. ATM Controls Genomic Stability in Pluripotent Stem Cells
    JASON MARK BECKTA; Fiscal Year: 2013
    ..ATM, a serine-threonine kinase, plays a major role in many intracellular signaling networks, such as the DNA damage response...
  43. The Role of CD5 in B-Cell Development and Autoimmunity
    Chander Raman; Fiscal Year: 2012
    ..The survival activity of CD5 is mediated its unique interaction with CK2, a serine/threonine kinase that is a major positive regulator of multiple cellular prosurvival signaling cascades...
  44. Studying a novel regulator of GBM tumorigeneis: the role of CK2alpha in maintaini
    Gordon Li; Fiscal Year: 2013
    ..My studies focus on the role of casein kinase 2 (CK2), a highly conserved pleiotropic serine/threonine kinase that has been associated with cell survival in many cancers...
  45. Zot, Zonulin, and Pathophysiology of Intestinal Tight Junctions
    Alessio Fasano; Fiscal Year: 2013
    ..We have demonstrated that this transactivation is followed by protein kinase C (PKC)a-mediated ZO-1 and myosin 1c serine/threonine phosphorylation, provoking ZO-1 disengagement from three of its binding partners, occludin, claudin-1, ..
  46. MNEI/SerpinB1: A modulator of innate pulmonary defense
    EILEEN REMOLD-O'DONNELL; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The neutrophil serine proteases (NSPs) (elastase, cathepsin G and proteinase-3) released at inflammatory sites by degranulating or necrotic neutrophils are major contributors to the pathology of ..
  47. Chromosomal Control of Segregation of C. Elegans
    Abby F Dernburg; Fiscal Year: 2013
    ..to identify meiotic components and regulatory mechanisms, we will build on the knowledge that three conserved serine/threonine kinases, CHK-2, PLK-2, and AIR-2, play essential regulatory roles in meiosis...
  48. The Role of PKR in a Novel IL-3 Signal Transduction Pathway
    William Stratford May; Fiscal Year: 2012
    ..Significantly, our findings reveal that RAX phosphorylation on serine 18 is required for PKR activation, translation inhibition and apoptosis initiated by diverse cellular stresses...
  49. Functional Analysis of the Dual Specificity Kinase NEK1 in Mammalian Meiosis
    JOANNA KIM HOLLOWAY; Fiscal Year: 2013
    ..NEK1 is a dual activity serine/threonine and tyrosine kinase, and is highly expressed in germ cells, particularly the narrow window encompassing ..
  50. Using Mass Spectroscopy to Characterize Transcription Proteins and F2-Isoprostane
    BETTYE HENNINTON; Fiscal Year: 2011
    ..A comparison of the sequences of MLL3 and Gcrlp indicates that MLL3 also has serine-proline-rich regions in similar areas of the amino acid sequence...
  51. Lipid glyceryl ester homeostasis in macrophages and perturbation by environmental
    Matthew K Ross; Fiscal Year: 2012
    ..An enzyme (Mr 31-32kDa) of un- known function was also detected by serine hydrolase activity profiling and may be responsible for the remaining glyceryl ester hydrolysis activity...
  52. Characterization of the thioredoxins system in the diabetic retina
    Folami Lamoke; Fiscal Year: 2013
    ..We have recently found that hyperglycemia promotes TXNIP serine phosphorylation (SerP)...
  53. Pulmonary Vascular-Right Ventricular Axis Research Program
    Wai Hong Wilson Tang; Fiscal Year: 2013
    ..Activation of eNOS requires enzyme dephosphorylation at Threonine 495 (T495) and phosphorylation at Serine 1177 (S1177), the latter mediated by cyclic adenosine monophosphate (cAMP)/protein kinase pathways downstream of ?-..
  54. Metal Exposure and Children?s Preschool Neurodevelopment
    David C Bellinger; Fiscal Year: 2012
    ..methylenetetrahydrofolate reductase, GST- M1, T1, P1, omega, purine nucleoside phosphorylase, cytosolic serine hydroxymethyltransferase)...
  55. Global Regulation of Gene expression in Streptococcus pneumoniae
    Bernard Weisblum; Fiscal Year: 2010
    ..The proposed studies will focus on the response regulator RitR, on a Serine/Threonine kinase phosphatase pair, and on their mutual interactions...
  56. Microvascular Dysfunction in Hyperhomocysteinemia
    Shawn E Bearden; Fiscal Year: 2012
    ..Pilot data show that homocysteine disrupts CVD and increases serine phosphorylation of both connexin40 and connexin43, which are responsible for endothelial cell-cell (EC-EC) and ..
  57. Mineralocorticoid Receptor-Mediated Vascular Insulin Resistance
    SHAWN BRADY BENDER; Fiscal Year: 2013
    ..acting via several mechanisms including oxidative stress, fibrosis, endothelial dysfunction and activation of serine kinases such as Rho kinase (ROK)...
  58. SFRP2 and NFAT are therapeutic targets in angiosarcoma
    NANCY K DEMORE; Fiscal Year: 2013
    ..balance between the activity of the Ca2+/calmodulin-dependent phosphatase, calcineurin, and the activity of serine/threonine kinases(20)...
  59. Cell death regulation in proteotoxic therapy
    Wei Xing Zong; Fiscal Year: 2013
    ..We also reported that an endogenous serine/cysteine protease inhibitor SerpinB3 (also termed squamous cell carcinoma antigen 1, SCCA1) may function as a ..
  60. Enzymology of Chlamydia Pathogenesis
    Dewey G McCafferty; Fiscal Year: 2013
    ..Of these effectors, the serine protease chlamydial protease-like activity factor (CPAF) is an enzyme that has emerged as a central virulence ..
  61. Cx43 phosphorylation modulates Kras mediated pancreas cancer progression
    Paul D Lampe; Fiscal Year: 2012
    ..Cx43, by far the most widely expressed connexin (>34 tissues and 46 cell types), is phosphorylated at multiple serine residues found in the cytoplasmic, C-terminal region...
  62. Dysfunctional PGC-1alpha expression in skeletal muscle during diabetes
    S Russ Price; Fiscal Year: 2013
    ..from abnormal signaling through one or more pathways that are regulated by calcineurin (Cn), a calcium-activated serine/threonine phosphatase...
  63. Plasminogen activators and NMDA after brain injury
    William M Armstead; Fiscal Year: 2012
    ..Urokinase and tissue plasminogen activator (uPA and tPA) are serine proteases whose contributions to the regulation of cerebral hemodynamics are not well characterized...
  64. Tpl2 in Carcinogenesis-Related Inflammation
    KATHLEEN LEIGH DECICCO-SKINNER; Fiscal Year: 2011
    ..We propose to examine the mechanism by which tumor progression locus 2 (Tpl2), a serine/threonine kinase in the MAPK signal transduction cascade, affects skin cancer development by analyzing the ..
  65. BIOSYNTHESIS OF COMPLEX CARBOHYDRATES IN BRAIN
    LENNART RODEN; Fiscal Year: 1993
    ..Substrates of two types will be prepared: (1) serine-linked oligosaccharides will be synthesized chemically and (2) macromolecular substrates which are more akin to ..
  66. EFFECTS OF ETHANOL ON PHOSPHOLIPASE D MEDIATED SIGNALING
    Joel Horwitz; Fiscal Year: 2003
    ..data demonstrate that all the agents that activate phospholipase D, also cause phosphorylation of the enzyme on serine residues. Inhibition of serine phosphatase enhances BK stimulated phospholipase D...
  67. STUDIES OF NEURONAL AND GLIAL GLUTAMATE DECARBOXYLASES
    Jang Yen Wu; Fiscal Year: 1990
    ..gamma-aminobutyric acid (GABA), glycine, aspartate/glutamate, and taurine, namely L-glutamate decarboxylase (GAD), serine transhydroxymethylase (serine-THM), cysteinesulfinic and cyteic acids decarboxylase (CSAD/CAD) and aspartate amino ..
  68. Serine Proteinase Inhibitors (Serpins) in Tick Feeding and Physiology
    Albert Mulenga; Fiscal Year: 2009
    ..One important such class of proteins, are serine proteinase inhibitors that are commonly referred to by its acronym "serpin", which is the largest class of ..
  69. ONTOGENY OF FETAL HEPATIC SERINE AND GLYCINE METABOLISM
    Michael Narkewicz; Fiscal Year: 1999
    ..We have focused our studies on serine and glycine, two amino acids with unique fetal characteristics...
  70. ENTEROBACTIN DERIVATIVES: BUILDING A BETTER FERRIC TRAP
    Carlos Gutierrez; Fiscal Year: 1991
    ..coli, exhibits the largest binding constant fo ferric ion of any natural substance. It is composed a tri-L-serine lactone nucleus to which are appended three exocyclic 2,3-dihydroxybenzamide units which serve as the binding ..
  71. FUNCTION OF FACTOR VIII ON THE PLATELET MEMBRANE
    Gary Gilbert; Fiscal Year: 2001
    ..acidic phospholipid, resembling cell membranes, factor VIII exhibits stereoselective affinity for phosphatidyl-L-serine containing binding sites...
  72. BIOPHYSICS OF SERINE PROTEASE-KUNITZ INHIBITOR COMPLEXES
    Gaetano Montelione; Fiscal Year: 1999
    ..the structure-function relationships and interfacial dynamics of Kunitz-type protease inhibitors complexed with serine proteases...