Summary: An essential branched-chain amino acid important for hemoglobin formation.

Top Publications

  1. ncbi CRM1 is an export receptor for leucine-rich nuclear export signals
    M Fornerod
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1051-60. 1997
  2. ncbi Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
    Jung Min Han
    Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151 742, Republic of Korea
    Cell 149:410-24. 2012
  3. ncbi Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters
    Atsuko Yamashita
    Department of Biochemistry and Molecular Biophysics and
    Nature 437:215-23. 2005
  4. pmc Bidirectional transport of amino acids regulates mTOR and autophagy
    Paul Nicklin
    Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Novartis Horsham Research Centre, West Sussex, UK
    Cell 136:521-34. 2009
  5. ncbi Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
    J P Hugot
    Fondation Jean Dausset CEPH, 27 rue J Dodu 75010 Paris, France
    Nature 411:599-603. 2001
  6. pmc L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway
    Elspeth M Payne
    Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 120:2214-24. 2012
  7. ncbi Hypothalamic mTOR signaling regulates food intake
    Daniela Cota
    Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA
    Science 312:927-30. 2006
  8. pmc Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans
    Renato V Iozzo
    Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    FEBS J 277:3864-75. 2010
  9. pmc Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism
    Yazmin Macotela
    Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e21187. 2011
  10. ncbi Analysis and prediction of leucine-rich nuclear export signals
    Tanja la Cour
    Center for Biological Sequence Analysis, BioCentrum DTU, Technical University of Denmark, Building 208, DK 2800 Lyngby, Denmark
    Protein Eng Des Sel 17:527-36. 2004

Detail Information

Publications368 found, 100 shown here

  1. ncbi CRM1 is an export receptor for leucine-rich nuclear export signals
    M Fornerod
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1051-60. 1997
    ..We conclude that CRM1 is an export receptor for leucine-rich nuclear export signals and discuss a model for the role of RanGTP in CRM1 function and in nuclear export in ..
  2. ncbi Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
    Jung Min Han
    Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151 742, Republic of Korea
    Cell 149:410-24. 2012
    ..synthetase (LRS) plays a critical role in amino acid-induced mTORC1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mTORC1 activation...
  3. ncbi Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters
    Atsuko Yamashita
    Department of Biochemistry and Molecular Biophysics and
    Nature 437:215-23. 2005
    ..structure of a bacterial homologue of these transporters from Aquifex aeolicus, in complex with its substrate, leucine, and two sodium ions...
  4. pmc Bidirectional transport of amino acids regulates mTOR and autophagy
    Paul Nicklin
    Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Novartis Horsham Research Centre, West Sussex, UK
    Cell 136:521-34. 2009
    ..a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells...
  5. ncbi Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
    J P Hugot
    Fondation Jean Dausset CEPH, 27 rue J Dodu 75010 Paris, France
    Nature 411:599-603. 2001
    ..These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region...
  6. pmc L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway
    Elspeth M Payne
    Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 120:2214-24. 2012
    ..RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation...
  7. ncbi Hypothalamic mTOR signaling regulates food intake
    Daniela Cota
    Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA
    Science 312:927-30. 2006
    ..Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight...
  8. pmc Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans
    Renato V Iozzo
    Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    FEBS J 277:3864-75. 2010
    The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease...
  9. pmc Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism
    Yazmin Macotela
    Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e21187. 2011
    ..In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism...
  10. ncbi Analysis and prediction of leucine-rich nuclear export signals
    Tanja la Cour
    Center for Biological Sequence Analysis, BioCentrum DTU, Technical University of Denmark, Building 208, DK 2800 Lyngby, Denmark
    Protein Eng Des Sel 17:527-36. 2004
    ..We employ both neural networks and hidden Markov models in the prediction algorithm and verify the method on the most recently discovered NESs. The NES predictor (NetNES) is made available for general use at http://www.cbs.dtu.dk/...
  11. ncbi Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
    Daniel Cuthbertson
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, Scotland
    FASEB J 19:422-4. 2005
    ..Countermeasures to maximize muscle maintenance should target these deficits...
  12. pmc Occurrence of the leucine-to-phenylalanine knockdown resistance (kdr) mutation in Anopheles arabiensis populations in Tanzania, detected by a simplified high-throughput SSOP-ELISA method
    Manisha A Kulkarni
    Department of Natural Resource Sciences, McGill University, Macdonald Campus, Ste Anne de Bellevue, Quebec H9X 3V9, Canada
    Malar J 5:56. 2006
    ..Knockdown resistance (kdr) confers resistance to the pyrethroid class of insecticides with cross-resistance to DDT through single nucleotide polymorphisms (SNPs) in the voltage-gated sodium channel gene...
  13. pmc The root knot nematode resistance gene Mi from tomato is a member of the leucine zipper, nucleotide binding, leucine-rich repeat family of plant genes
    S B Milligan
    Center for Engineering Plants for Resistance Against Pathogens, University of California, Davis, California 95616, USA
    Plant Cell 10:1307-19. 1998
    ..Prf and Mi-1.2 share several structural motifs, including a nucleotide binding site and a leucine-rich repeat region, that are characteristic of a family of plant proteins, including several that are required ..
  14. pmc Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites
    Michael Povelones
    Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK
    Science 324:258-61. 2009
    b>Leucine-rich repeat-containing proteins are central to host defense in plants and animals...
  15. pmc Structural basis for leucine-rich nuclear export signal recognition by CRM1
    Xiuhua Dong
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390 9041, USA
    Nature 458:1136-41. 2009
    ..known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 A structure of CRM1 bound to snurportin 1 (SNUPN)...
  16. pmc Effects of a leucine and pyridoxine-containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects
    Michael B Zemel
    NuSirt Sciences, Knoxville, TN 37931, USA
    Nutrients 4:529-41. 2012
    b>Leucine stimulates tissue protein synthesis and may also attenuate adiposity by increasing fatty acid oxidation and mitochondrial biogenesis in muscle and adipocytes. Accordingly, the effects of a nutraceutical containing 2...
  17. pmc Dynamic nucleotide-binding site and leucine-rich repeat-encoding genes in the grass family
    Sha Luo
    Key Laboratory of Horticulture Biology, Ministry of Education, and Department of Vegetable Crops, College of Horticulture and Forestry, Huazhong Agricultural University, Wuhan, People s Republic of China, 430070
    Plant Physiol 159:197-210. 2012
    ..We analyzed genes encoding nucleotide-binding sites and leucine-rich repeats in the genomes of rice (Oryza sativa), maize (Zea mays), sorghum (Sorghum bicolor), and Brachypodium ..
  18. pmc Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach
    Gilbert Zeanandin
    Centre Hospitalier Universitaire de Nice, pole digestif, Nice, France
    Age (Dordr) 34:371-87. 2012
    b>Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia...
  19. ncbi The leucine-rich repeat as a protein recognition motif
    B Kobe
    Department of Biochemistry and Molecular Biology Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Queensland, Australia
    Curr Opin Struct Biol 11:725-32. 2001
    b>Leucine-rich repeats (LRRs) are 20-29-residue sequence motifs present in a number of proteins with diverse functions...
  20. pmc A competitive inhibitor traps LeuT in an open-to-out conformation
    Satinder K Singh
    Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
    Science 322:1655-61. 2008
    ..We used crystallographic and functional studies on the leucine transporter (LeuT), a model for neurotransmitter sodium symporters, to show that various amino acid substrates ..
  21. ncbi A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly
    Christos S Katsanos
    Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77550, USA
    Am J Physiol Endocrinol Metab 291:E381-7. 2006
    This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals...
  22. ncbi Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis
    Scot R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA, USA
    J Nutr 136:227S-31S. 2006
    ..Of the three BCAAs, leucine is the one primarily responsible for the stimulation of protein synthesis under these circumstances...
  23. pmc LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake
    Zheng Zhou
    Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Science 317:1390-3. 2007
    ..We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine...
  24. ncbi Oral leucine administration stimulates protein synthesis in rat skeletal muscle
    Stephen J Crozier
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 135:376-82. 2005
    Oral administration of a single bolus of leucine in an amount equivalent to the daily intake (1.35 g/kg body wt) enhances skeletal muscle protein synthesis in food-deprived rats...
  25. pmc MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA
    Jianmin Meng
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 285:27935-43. 2010
    ..Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A)...
  26. pmc The mechanism of a neurotransmitter:sodium symporter--inward release of Na+ and substrate is triggered by substrate in a second binding site
    Lei Shi
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Mol Cell 30:667-77. 2008
    ..The crystal structure of LeuT(Aa), a prokaryotic NSS homolog, revealed an occluded state in which one leucine and two Na(+) ions are bound, but provided limited clues to the molecular mechanism of transport...
  27. pmc Defective regulation of autophagy upon leucine deprivation reveals a targetable liability of human melanoma cells in vitro and in vivo
    Joon Ho Sheen
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cancer Cell 19:613-28. 2011
    Autophagy is of increasing interest as a target for cancer therapy. We find that leucine deprivation causes the caspase-dependent apoptotic death of melanoma cells because it fails to appropriately activate autophagy...
  28. pmc Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit
    J C Bryant
    Department of Pharmacology, Room 424 MRB1, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Biochem J 339:241-6. 1999
    Methylation of the C-terminal leucine residue (Leu309) of protein serine/threonine phosphatase 2A catalytic subunit (PP2AC) is known to regulate catalytic activity in vitro, but the functional consequence(s) of this post-translational ..
  29. ncbi Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis
    Stefan M Pasiakos
    Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA
    Am J Clin Nutr 94:809-18. 2011
    ..ie, endurance) exercise on postexercise skeletal muscle metabolism are not well described, and the potential role of supplemental leucine on muscle protein synthesis (MPS) and associated molecular responses remains to be elucidated.
  30. ncbi Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice
    Anne Freudenberg
    German Institute of Human Nutrition in Potsdam Rehbruecke DIfE, Arthur Scheunert Allee 114 116, 14558 Nuthetal, Germany
    J Nutr Biochem 23:1524-30. 2012
    ..We aimed to study whether leucine supplementation is able to mimic the alleviating effects of high-protein diets on metabolic syndrome parameters ..
  31. pmc Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein
    Shanon L Casperson
    Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
    Clin Nutr 31:512-9. 2012
    ..Protein-energy supplementation is routinely employed to combat muscle loss. However, success is often compromised by increased satiety, poor palatability, high costs and low compliance...
  32. ncbi Leucine and mTORC1: a complex relationship
    Kayleigh M Dodd
    Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, Wales, UK
    Am J Physiol Endocrinol Metab 302:E1329-42. 2012
    ..The branched-chain amino acid leucine is critical for muscle growth and acts in part through activation of mTORC1...
  33. pmc Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing
    Hugues Magne
    Clermont Universite, Universite d Auvergne, Unite de Nutrition Humaine, BP 10448, F 63000 Clermont Ferrand, France
    J Physiol 590:2035-49. 2012
    ..This study was conducted to explore protein synthesis during reloading and leucine supplementation effect as a nutritional strategy for muscle recovery...
  34. pmc Hypothalamic leucine metabolism regulates liver glucose production
    Ya Su
    Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, USA
    Diabetes 61:85-93. 2012
    ..Specifically, we tested the novel hypothesis that the metabolism of leucine within the MBH couples the central sensing of leucine with the control of glucose production by the liver...
  35. ncbi Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats
    Gabriel J Wilson
    Division of Nutritional Sciences, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Am J Physiol Endocrinol Metab 301:E1236-42. 2011
    ..This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal...
  36. pmc Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation
    Matthias Quick
    Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 106:5563-8. 2009
    ..structure of the neurotransmitter/sodium symporter homolog LeuT revealed an occluded binding pocket containing leucine and 2 Na(+); later structures showed tricyclic antidepressants (TCAs) in an extracellular vestibule approximately ..
  37. ncbi A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction
    J Li
    Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 90:929-38. 1997
    ..It encodes a ubiquitously expressed putative receptor kinase. The extracellular domain contains 25 tandem leucine-rich repeats that resemble repeats found in animal hormone receptors, plant disease resistance genes, and genes ..
  38. pmc Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters
    Derek P Claxton
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Nat Struct Mol Biol 17:822-9. 2010
    ..the dynamics of LeuT in the region of the extracellular vestibule associated with the binding of Na(+) and leucine. The results outline the Na(+)-dependent formation of a dynamic outward-facing intermediate that exposes the ..
  39. ncbi Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms
    Yiying Zhang
    Department of Pediatrics, Division of Molecular Genetics, Columbia University, New York, NY 10032, USA
    Diabetes 56:1647-54. 2007
    b>Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism...
  40. pmc Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women
    Erin L Glynn
    Departments of Physical Therapy, University of Texas Medical Branch, Galveston, TX 77555, USA
    J Nutr 140:1970-6. 2010
    Essential amino acids (EAA) stimulate skeletal muscle protein synthesis (MPS) in humans. Leucine may have a greater stimulatory effect on MPS than other EAA and/or decrease muscle protein breakdown (MPB)...
  41. ncbi Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers
    T W Hai
    Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138
    Genes Dev 3:2083-90. 1989
    ..All ATF cDNA clones examined contain a leucine zipper motif and are significantly similar to one another only within this region...
  42. ncbi Cutting edge: CATERPILLER: a large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains
    Jonathan A Harton
    Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Immunol 169:4088-93. 2002
    Large mammalian proteins containing a nucleotide-binding domain (NBD) and C-terminal leucine-rich repeats (LRR) similar in structure to plant disease resistance proteins have been suggested as critical in innate immunity...
  43. pmc Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle
    Hans C Dreyer
    Department of Physical Therapy, Division of Rehabilitation Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 1144, USA
    Am J Physiol Endocrinol Metab 294:E392-400. 2008
    ..we hypothesized that enhanced mTOR signaling might be responsible for the greater muscle protein synthesis when leucine-enriched EAA+CHOs are ingested during postexercise recovery...
  44. pmc Deletion of v7-3 (SLC6A15) transporter allows assessment of its roles in synaptosomal proline uptake, leucine uptake and behaviors
    Jana Drgonova
    Molecular Neurobiology Branch, NIDA, NIH, 333 Cassell Drive, Baltimore, MD 21224, USA
    Brain Res 1183:10-20. 2007
    ..into cortical synaptosomes of v7-3 knockouts identified 15% and 40% reductions in sodium-dependent proline and leucine transport, respectively, compared to wild type controls...
  45. ncbi Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system
    K S Fong
    Department of Zoology, University of Hawaii at Manoa, Honolulu, Hawaii, 96822, USA
    Genomics 58:146-57. 1999
    The flightless-I gene encodes a member of the gelsolin-like family of actin-binding proteins linked to a leucine-rich repeat (LRR) domain...
  46. ncbi A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss
    Eduardo R Ropelle
    Department of Internal Medicine, State University of Campinas UNICAMP, 13083 970, Campinas, Sao Paulo, Brazil
    Diabetes 57:594-605. 2008
    ..Here, we sought to determine whether the response of the AMPK and mTOR pathways could contribute to the molecular effects of an HPD...
  47. pmc Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine
    Charles H Lang
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 298:E1283-94. 2010
    ..assessed in wild-type (WT) and mTOR heterozygous (+/-) mice under basal conditions and in response to LPS and/or leucine stimulation...
  48. pmc Leucine supplementation protects from insulin resistance by regulating adiposity levels
    Elke Binder
    INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, Bordeaux, France Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, Bordeaux, France
    PLoS ONE 8:e74705. 2013
    b>Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear...
  49. ncbi Leucine suppresses myofibrillar proteolysis by down-regulating ubiquitin-proteasome pathway in chick skeletal muscles
    Kazuki Nakashima
    Department of Animal Physiology and Nutrition, National Institute of Livestock and Grassland Science, Tsukuba 305 0901, Japan
    Biochem Biophys Res Commun 336:660-6. 2005
    In skeletal muscle, amino acids, together with hormones, are key regulators of protein metabolism. Leucine, in particular, has inhibitory effects of protein degradation in skeletal muscles, but the mechanisms are poorly understood...
  50. ncbi Identification of the aceA gene encoding isocitrate lyase required for the growth of Pseudomonas aeruginosa on acetate, acyclic terpenes and leucine
    Alma Laura Díaz-Pérez
    Instituto de Investigaciones Quimico Biologicas, Universidad Michoacana de San Nicolas de Hidalgo, Morelia, Michoacan, Mexico
    FEMS Microbiol Lett 269:309-16. 2007
    ..ICL enzyme activity in crude extracts from cultures of the PAO1 strain was induced by acetate, citronellol and leucine, and repressed by growth on glucose or citrate...
  51. pmc Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice
    Hongliang Li
    Section of Molecular Medicine, Dept of Medicine, Univ of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Am J Physiol Endocrinol Metab 303:E1234-44. 2012
    b>Leucine supplementation has been shown to prevent high-fat diet (HFD)-induced obesity, hyperglycemia, and dyslipidemia in animal models, but the underlying mechanisms are not fully understood...
  52. ncbi Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia
    Pekka Jaako
    Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden
    Blood 120:2225-8. 2012
    ..a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for ..
  53. pmc The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly
    Shoujun Chen
    Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612 4799, USA
    FEBS J 280:2120-37. 2013
    Small leucine-rich proteoglycans (SLRPs) are involved in a variety of biological and pathological processes. This review focuses on their regulatory roles in matrix assembly...
  54. ncbi Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region
    J Wu
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA
    J Biol Chem 270:14209-13. 1995
    ..Nup358 contains a leucine-rich region, four potential Ran binding sites (i.e...
  55. ncbi Dietary leucine improves whole-body insulin sensitivity independent of body fat in diet-induced obese Sprague-Dawley rats
    Lindsay K Eller
    Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4
    J Nutr Biochem 24:1285-94. 2013
    ..The specific components of dairy responsible for these actions are not known but may include leucine. Our objective was to determine the effect of dietary protein (casein, skim milk or leucine) and Ca level [low, 0...
  56. pmc Histone deacetylase 3 suppression increases PH domain and leucine-rich repeat phosphatase (Phlpp)1 expression in chondrocytes to suppress Akt signaling and matrix secretion
    Elizabeth W Bradley
    Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 288:9572-82. 2013
    ..These data demonstrate that Hdac3 controls chondrocyte hypertrophy and matrix content by repressing Phlpp1 expression and facilitating Akt activity...
  57. pmc Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism
    D J Wilkinson
    Metabolic and Molecular Physiology Research Group, MRC ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Graduate Entry Medicine and Health, Derby DE22 3DT, UK
    J Physiol 591:2911-23. 2013
    ..Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of ..
  58. ncbi Leucine-rich nuclear-export signals: born to be weak
    Ulrike Kutay
    Swiss Federal Institute of Technology ETH Zurich, Institute of Biochemistry, Schafmattstrasse 18, HPM F11 1, 8093 Zurich, Switzerland
    Trends Cell Biol 15:121-4. 2005
    CRM1 mediates the nuclear export of proteins exposing leucine-rich nuclear-export signals (NESs). Most NESs bind to CRM1 with relatively low affinity. Recently, higher-affinity NESs were selected from a 15-mer random peptide library...
  59. ncbi Effect of Leucine and Lysine substitution on the antimicrobial activity and evaluation of the mechanism of the HPA3NT3 analog peptide
    Ramamourthy Gopal
    Research Center for Proteineous Materials RCPM, Chosun University, Gwangju, Korea
    J Pept Sci 15:589-94. 2009
    ..These results suggest that the substitutions of Arg and Asn with Lys and two Trp with Leu resulted in small changes in HPA3NT3-analog activity and significant decreases in hemolytic activity...
  60. pmc Activation of an Arabidopsis resistance protein is specified by the in planta association of its leucine-rich repeat domain with the cognate oomycete effector
    Ksenia V Krasileva
    Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA
    Plant Cell 22:2444-58. 2010
    ..The leucine-rich repeat (LRR) domain of RPP1 mediates the interaction with ATR1, while the Toll/Interleukin1 Receptor (TIR) ..
  61. ncbi An overview of the therapeutic effects of leucine supplementation on skeletal muscle under atrophic conditions
    Humberto Nicastro
    Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sports, University of Sao Paulo, Sao Paulo, Brazil
    Amino Acids 40:287-300. 2011
    ..Among anti-atrophic therapies, amino acid supplementation, particularly with leucine, has received a lot of attention...
  62. ncbi Paxillin associates with the microtubule cytoskeleton and the immunological synapse of CTL through its leucine-aspartic acid domains and contributes to microtubule organizing center reorientation
    Leslie K Robertson
    Department of Medical Microbiology and Immunology, University of Alberta, Edmonton T6G 2S2, Alberta, Canada
    J Immunol 187:5824-33. 2011
    ..We mapped the region of paxillin that associates with both the MTOC and SMAC to the leucine-aspartic acid (LD) domains and showed that a protein segment containing LD2-4 was sufficient for MTOC and SMAC ..
  63. ncbi Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer
    Hiroshi Uchida
    Department of Pathology, School of Medicine, Keio University, Tokyo, Japan
    Cancer Sci 101:1731-7. 2010
    b>Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a 7-transmembrane receptor reportedly expressed in stem cells of the intestinal crypts and hair follicles of mice...
  64. ncbi Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain
    H Xie
    Department of Chemistry and Biochemistry, University of California, Los Angeles 90024 1569
    J Biol Chem 269:1981-4. 1994
    ..40-kDa methyl-transferase, results in the methyl esterification of the alpha-carboxyl group of the C-terminal leucine residue. We have now purified the major methylated 36-kDa polypeptide from bovine brain...
  65. ncbi Potential importance of leucine in treatment of obesity and the metabolic syndrome
    Donald K Layman
    Division of Nutritional Sciences, University of Illinois, Urbana, IL 16801, USA
    J Nutr 136:319S-23S. 2006
    ..between dietary protein and carbohydrates are the relationships between the branched-chain amino acid leucine and insulin and glucose metabolism...
  66. pmc Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism
    Pengxiang She
    Dept of Cellular and Molecular Physiology, MC H166, Penn State Univ College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 293:E1552-63. 2007
    ..Our results are consistent with the idea that tissue-specific alterations in BCAA metabolism, in liver and adipose tissue but not in muscle, may contribute to the rise in plasma BCAAs in obesity...
  67. ncbi Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
    N T Bech-Hansen
    Department of Medical Genetics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    Nat Genet 26:319-23. 2000
    ..encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family...
  68. pmc Diversity in nucleotide binding site-leucine-rich repeat genes in cereals
    Jianfa Bai
    Department of Plant Pathology, Kansas State University, Manhattan, Kansas 66506 5502, USA
    Genome Res 12:1871-84. 2002
    The diversity of the largest group of plant disease resistance genes, the nucleotide binding site-leucine-rich repeat (NBS-LRR) genes, was examined in cereals following polymerase chain reaction (PCR) cloning and database mining...
  69. pmc NESbase version 1.0: a database of nuclear export signals
    Tanja la Cour
    Center for Biological Sequence Analysis, Building 208, Technical University of Denmark, DK 2800 Lyngby, Denmark
    Nucleic Acids Res 31:393-6. 2003
    Protein export from the nucleus is often mediated by a Leucine-rich Nuclear Export Signal (NES). NESbase is a database of experimentally validated Leucine-rich NESs curated from literature...
  70. ncbi Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 274:11647-52. 1999
    ..In the present study, leucine stimulated phosphorylation of the eIF4E-binding protein, 4E-BP1, in L6 myoblasts, resulting in dissociation of ..
  71. ncbi The role of small leucine-rich proteoglycans in collagen fibrillogenesis
    Sebastian Kalamajski
    Lund University, Department of Experimental Medical Science, BMC B12, Lund, Sweden
    Matrix Biol 29:248-53. 2010
    Small leucine-rich proteoglycans/proteins (SLRPs) are associated with collagen fibril formation, and therefore important for the proper formation of extracellular matrices...
  72. ncbi The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats
    Layne E Norton
    Division of Nutritional Sciences, Department of Food Science and Human Nutrition, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    J Nutr 139:1103-9. 2009
    This study examined the impact of leucine (Leu) derived from complete meals on stimulation of skeletal muscle protein synthesis (MPS). Expt. 1 examined time course changes in translation initiation and MPS after a meal...
  73. ncbi RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family
    K Miyake
    Department of Immunology, Saga Medical School, Japan
    J Immunol 154:3333-40. 1995
    ..The RP105 molecule possesses 22 tandem repeats of a leucine-rich motif...
  74. ncbi Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer
    Sandra Troup
    Department of Pathology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, R3E OW3 Canada
    Clin Cancer Res 9:207-14. 2003
    To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma.
  75. ncbi A novel gene family encoding leucine-rich repeat transmembrane proteins differentially expressed in the nervous system
    Juha Lauren
    Program in Molecular Neurobiology, Institute of Biotechnology, University of Helsinki, P O Box 56 Viikinkaari 9, FIN 00014 Helsinki, Finland
    Genomics 81:411-21. 2003
    b>Leucine-rich repeat containing proteins are involved in protein-protein interactions and they regulate numerous cellular events during nervous system development and disease...
  76. pmc Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis
    Xiaoping Tan
    The Genome Center, University of California, Davis, California 95616, USA
    BMC Plant Biol 7:56. 2007
    Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0...
  77. pmc Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production
    Tobias Moehlmann
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8025-30. 2002
    ..Finally, we show that PS1 L166 mutants affect the generation of NICD and AICD in a similar manner, supporting the concept that S3 protease and S3-like gamma-secretase cleavages are mediated by identical proteolytic activities...
  78. pmc Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity
    Sushma J Bhakta
    Emory Vaccine Center at the Yerkes National Primate Research Center and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30329, USA
    Retrovirology 8:37. 2011
    ..Additional mutants targeting individual motifs were then constructed...
  79. pmc Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit
    Clemence Blouet
    Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA
    J Neurosci 29:8302-11. 2009
    ..While central leucine reduces food intake and body weight, the specific neuroanatomical sites of leucine sensing, downstream neural ..
  80. pmc Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle
    Asish K Saha
    Diabetes Research Unit, Division of Endocrinology, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA
    Diabetes 59:2426-34. 2010
    Branched-chain amino acids, such as leucine and glucose, stimulate protein synthesis and increase the phosphorylation and activity of the mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase (p70S6K)...
  81. pmc Both the extracellular leucine-rich repeat domain and the kinase activity of FSL2 are required for flagellin binding and signaling in Arabidopsis
    L Gomez-Gomez
    Friedrich Miescher Institut, P O Box 2543, CH 4002 Basel, Switzerland
    Plant Cell 13:1155-63. 2001
    ..domain of flagellin, represented by the peptide flg22, in a process involving the FLS2 gene, which encodes a leucine-rich repeat serine/threonine protein kinase...
  82. pmc The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction
    Yumiko Mizutori
    Autoimmune Disease Unit, Cedars Sinai Research Institute, University of California, Los Angeles, California 90048, USA
    Mol Endocrinol 22:1171-82. 2008
    The glycoprotein hormone receptor hinge region connects the leucine-rich and transmembrane domains. The prevalent concept is that the hinge does not play a significant role in ligand binding and signal transduction...
  83. pmc Leucine-rich repeat transmembrane proteins instruct discrete dendrite targeting in an olfactory map
    Weizhe Hong
    Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, California, USA
    Nat Neurosci 12:1542-50. 2009
    ..We found that the leucine-rich repeat (LRR) transmembrane protein Capricious (Caps) was differentially expressed in different classes of ..
  84. ncbi Leucine and protein synthesis: mTOR and beyond
    Martha H Stipanuk
    Division of Nutritional Sciences, 227 Savage Hall, Cornell University, Ithaca, NY 14853, USA
    Nutr Rev 65:122-9. 2007
    ..acid intake on protein synthesis in the intact rat appear to be mediated almost entirely by a single amino acid: leucine. The effect of leucine on protein synthesis appears to be closely associated with eIF4G phosphorylation and its ..
  85. pmc Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor
    David Dominguez
    Unitat de Biologia Cel lular i Molecular, Institut Municipal d Investigacio Medica, Universitat Pompeu Fabra, 08003 Barcelona, Spain
    Mol Cell Biol 23:5078-89. 2003
    ..These findings show the existence in tumor cells of an effective and fine-tuning nontranscriptional mechanism of regulation of Snail activity dependent on the extracellular environment...
  86. pmc Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia
    Isabelle Rieu
    Unite de Nutrition Humaine, UMR1019, Institut National de la Recherche Agronomique, Centre de Recherche, en Nutrition Humaine d Auvergne, F 63122 Saint Genes Champanelle, France
    J Physiol 575:305-15. 2006
    The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals...
  87. pmc Brassinosteroid-insensitive-1 is a ubiquitously expressed leucine-rich repeat receptor serine/threonine kinase
    D M Friedrichsen
    Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Plant Physiol 123:1247-56. 2000
    ..Screens for BR signaling mutants identified one locus, BRI1, which encodes a protein with homology to leucine-rich repeat receptor serine (Ser)/threonine (Thr) kinases...
  88. ncbi Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state
    Marie J Czikk
    Canadian Institute of Health Research Group in Fetal and Neonatal Health and Development, Department of Obstetrics and Gynaecology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada N6A 4V2
    Am J Physiol Regul Integr Comp Physiol 284:R200-7. 2003
    ..We have therefore determined the cerebral uptake of leucine and [(14)C]leucine during continuous tracer infusion as measures of leucine metabolism in relation to behavioral ..
  89. ncbi Select nutrients in the ovine uterine lumen. VII. Effects of arginine, leucine, glutamine, and glucose on trophectoderm cell signaling, proliferation, and migration
    Jin Young Kim
    Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A and M University, College Station, Texas 77843 2471, USA
    Biol Reprod 84:62-9. 2011
    ..Results from our laboratory indicate that arginine (Arg), leucine (Leu), glutamine (Gln), and glucose increase in the uterine lumen between Days 10 and 15 of pregnancy, coincident ..
  90. ncbi JLP associates with kinesin light chain 1 through a novel leucine zipper-like domain
    Quang Nguyen
    Fels Institute for Cancer Research and Molecular Biology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 280:30185-91. 2005
    ..JLP is a novel leucine zipper protein belonging to a family of scaffolding proteins that assemble JNK signaling modules...
  91. ncbi NtLRP1, a tobacco leucine-rich repeat gene with a possible role as a modulator of the hypersensitive response
    Alban Jacques
    Institut de Biologie Moleculaire des Plantes du CNRS, Universite Louis Pasteur, Strasbourg, France
    Mol Plant Microbe Interact 19:747-57. 2006
    ..Translation of the open reading frame of DD9-3 revealed a leucine-rich repeat (LRR) domain highly homologous with the receptor domain of a receptor kinase, suggesting a potential ..
  92. pmc Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle
    Jeffery Escobar
    USDA ARS Children s Nutrition Research Center, Dept of Pediatrics, Baylor College of Medicine, 1100 Bates St, Houston, TX 77030, USA
    Am J Physiol Endocrinol Metab 293:E1615-21. 2007
    We have previously shown that a physiological increase in plasma leucine for 60 and 120 min increases translation initiation factor activation in muscle of neonatal pigs...
  93. pmc A single conserved leucine residue on the first intracellular loop regulates ER export of G protein-coupled receptors
    Matthew T Duvernay
    Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112, USA
    Traffic 10:552-66. 2009
    ..These data indicate a crucial role for a single Leu residue within the ICL1 in ER export of GPCRs...
  94. ncbi Leucine as a pharmaconutrient to prevent and treat sarcopenia and type 2 diabetes
    Marika Leenders
    Top Institute Food and Nutrition TIFN, Wageningen, The Netherlands
    Nutr Rev 69:675-89. 2011
    ..These findings have been particularly pronounced for the amino acid leucine. Furthermore, leucine has the ability to act as a strong insulin secretagogue...
  95. pmc L-leucine alters pancreatic β-cell differentiation and function via the mTor signaling pathway
    Latif Rachdi
    INSERM U845, Research Center Growth and Signaling, Paris Descartes University, Sorbonne Paris Cité, Necker Hospital, Paris, France
    Diabetes 61:409-17. 2012
    b>Leucine (Leu) is an essential branched-chain amino acid, which activates the mammalian target of rapamycin (mTOR) signaling pathway. The effect of Leu on cell differentiation during embryonic development is unknown...
  96. ncbi Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine
    Gregory E R Weller
    Department of Bioengineering and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Cancer Res 65:533-9. 2005
    ..been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL)...
  97. ncbi N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinar
    Kevin S Thorneloe
    Cardiovascular and Urogenital Centre of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA
    J Pharmacol Exp Ther 326:432-42. 2008
    ..Overall TRPV4 plays an important role in urinary bladder function that includes an ability to contract the bladder as a result of the expression of TRPV4 in the UBSM...
  98. ncbi The central leucine-rich repeat region of chicken TLR16 dictates unique ligand specificity and species-specific interaction with TLR2
    A Marijke Keestra
    Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands
    J Immunol 178:7110-9. 2007
    ..in which the defined domains of chTLR16 and hTLR1 or hTLR6 had been exchanged revealed that the transfer of leucine-rich repeats (LRR) 6-16 of chTLR16 into hTLR6 was sufficient to confer dual ligand specificity to the human ..
  99. ncbi Leucine in food mediates some of the postprandial rise in plasma leptin concentrations
    Christopher J Lynch
    Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 291:E621-30. 2006
    ..at the level of mRNA translation by the rapamycin-sensitive mammalian target of rapamycin (mTOR) and its agonist leucine (Leu)...
  100. ncbi Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells
    L Deldicque
    Département d Education Physique et de Réadaptation, Universite Catholique de Louvain, Louvain la Neuve, Belgium
    Amino Acids 35:147-55. 2008
    This study compared the effects of leucine and glutamine on the mTOR pathway, on protein synthesis and on muscle-specific gene expression in myogenic C(2)C(12) cells...
  101. pmc Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site
    Chayne L Piscitelli
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 468:1129-32. 2010
    ..We conclude that LeuT harbours a single, centrally located, high-affinity substrate-binding site and that transport is well described by a simple, single-substrate kinetic mechanism...

Research Grants69

  1. Impact of the P479L Variant in CPT1A on Infant Mortality in Alaska
    David M Koeller; Fiscal Year: 2011
    ..1436C?T), which results in a proline to leucine substitution at amino acid 479 (p.P479L)...
  2. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2013
    ..kinase, a cellular scaffold/bridge for MEK/ERK/Elk activation, a nuclear transporter of ERK1/2 and hematin, a leucine-zipper (bZip) transcription factor, a regulator of TNF-1- activated kinase-mediator of autoimmunity and activator ..
    Thomas Ortel; Fiscal Year: 2010
    ..Tyrosine and leucine residues located in an analogous location within the homologous factor V C1 domain play a role in binding to ..
  4. Nutrition and Anabolic Interventions in Cancer Cachexia
    Melinda Sheffield-Moore; Fiscal Year: 2013
    ..affected because catabolic factors diminish the plasma concentrations of key branched-chain amino acids such as leucine, thereby suppressing the stimulus for nutrition-derived anabolism...
  5. Repression of PPARgamma-2 by Glucocorticoid-Induced Leucine Zipper
    Xing Ming Shi; Fiscal Year: 2012
    ..of this research is to address the question of how PPAR(2 expression can be repressed by glucocorticoid-induced leucine zipper (GILZ), a recently identified leucine zipper protein...
  6. The Mechanism of Cryptorchidism in LH Receptor Knockout Animals
    Zhenmin Lei; Fiscal Year: 2012
    ..alone did not significantly stimulate proliferation of gubernacular mesenchymal cells without activation of the leucine-rich repeat-containing G-protein coupled receptor 8 (LGR8) signaling pathway by addition of INSL3 or relaxin...
  7. Pulmonary Defenses Against Intracellular Infection
    Shawn J Skerrett; Fiscal Year: 2013
    ..Toll- like receptors (TLRs), which induce pro-inflammatory cytokines, and by cytosolic nucleotide-binding leucine rich repeat proteins (NLRs), which assemble inflammasomes that activates caspase-1...
  8. GILZ Regulation of ENaC
    David Pearce; Fiscal Year: 2012
    ..We recently identified the scaffolding protein, GILZ1 (glucocorticoid-induced leucine zipper protein, isoform 1), as an aldosterone-regulated gene product, which acts within distal nephron cells to ..
  9. The role of NLRP7 and related genes in hydatidiform moles and reproductive failur
    Ignatia Van den Veyver; Fiscal Year: 2009
    ..novel NLRP7 interactors by a saturated yeast-two-hybrid screen with the full-length NLRP7 protein and the NLRP7-leucine-rich repeat region...
    Steven A Fisher; Fiscal Year: 2013
    ..E23 skipping codes for a MYPT1 C-terminus leucine zipper (LZ) motif required for cGMP-dependent protein kinase (cGK1) dimerization and activation of MP, resulting ..
  11. Autoimmunity Against Novel Antigens in Neuropsychiatric Dysfunction
    Josep O Dalmau; Fiscal Year: 2013
    ..including among others the GluR1/2 subunits of the AMPA receptor (AMPAR), the GABA(B1) receptor (GABA(B1)R), Leucine rich glioma inactivated 1 (LGI1) and Contactin associated protein 2 (Caspr2)...
    Joseph Avruch; Fiscal Year: 2013
    ..functions, but regulation by the insulin/IGF system is superimposed on regulation by amino acids, especially leucine. In both yeast and man TOR functions in two physically distinct and independently regulated complexes;TOR complex ..
  13. Immunobiology of Acute Environmental Asthma
    David B Peden; Fiscal Year: 2013
    ..discovered the CATERPILLER family which share structural similarities with the NB-LRR (nucleotide-binding, leucine-rich repeat) super-family of disease resistance (R) proteins that constitutes the plant immune system...
  14. The Role of Beta-Gal Mediated Interactions in Prostate Cancer Metastasis
    VLADISLAV V GLINSKII; Fiscal Year: 2013
    ..been further hypothesized that inhibiting Gal-3 anti-apoptotic function using synthetic glycoamine Lactulosyl-L-Leucine (LL), will simultaneously target metastasis-associated adhesive events and augment sensitivity of metastatic ..
  15. Tumor drug delivery systems based on polymalic acid
    Julia Y Ljubimova; Fiscal Year: 2010
    ..endosomal disruption activity through enhanced hydrophobicity by exchange of valine in the present carrier with leucine ethylester thereby increasing membrane permeation;(b) exchanging the existing fluorescein reporter by Alexa Fluor ..
  16. Model systems for hematologic disorders caused by ribosomal protein deficiency
    George Thomas; Fiscal Year: 2010
    ..either small or large ribosomal subunit proteins;Aim2: Determine the effects of dexamethasone, lenalidomide, and leucine on the p53 response and on rpL5 and rpL11 translation in primary human hematopoietic cells depleted of ribosomal ..
  17. Eicosapentaenoic acid and protein modulation to induce anabolism in COPD
    MARIELLE PKJ ENGELEN; Fiscal Year: 2012
    ..EPA peak after intake, as well as the absence of anabolic agents like proteins and specific amino acids (ie leucine) might explain that EPA+DHA treatment was unsuccessful...
  18. Study of the HFE Transferrin Receptor interaction in mammalian iron homeostasis
    Paul Schmidt; Fiscal Year: 2010
    ..The L622A mutation disrupts a leucine residue that is essential for interaction between Hfe and Tfr1, but is not crucial for the Tfr1/Tf interaction...
  19. Recombinant Antibodies from the Sea Lamprey
    ZEEV contact PANCER; Fiscal Year: 2010
    ..VLRs consist of highly diverse leucine-rich repeat modules, which are assembled by DNA recombination via gene conversion, resulting in a potential ..
  20. Phenotypic Spectrum of LRRK2 Mutations
    Rachel Saunders-Pullman; Fiscal Year: 2013
    ..The discovery that mutations in the leucine rich repeat kinase kinase (LRRK2) gene comprise the most common monogenic etiology of Parkinson disease (PD) ..
  21. mt-Nd2 and Resistance to Autoimmune Diabetes
    Clayton E Mathews; Fiscal Year: 2013
    ..are not commonly associated with autoimmune Type 1 diabetes (T1D), although a C to A transversion resulting in a leucine to methonine substitution in the mt-ND2 gene has been associated with protection from T1D in both an at risk ..
  22. Definition of an Ancient T cell-like System in Lampreys
    MAX DALE COOPER; Fiscal Year: 2013
    ..conversion of incomplete germline VLR genes (VLRA, VLRB and VLRC) into fully assembled VLR genes using diverse leucine-rich-repeat (LRR) donor sequences...
  23. The Role of PcpA in the Mechanism of Virulence and Protective Immunity.
    MELISSA MARIE WALKER; Fiscal Year: 2013
    ..PcpA contains leucine-rich repeats (LRR)...
  24. Role of the Angiogenic Chemokine, CXCL5, in Prostate Cancer
    Liz Simon; Fiscal Year: 2012
    ..CXCL5 is a member of CXC family of chemokines with the three amino acid motif, glutamic acid-leucine-arginine (ELR+) and is a potent angiogenic promoter...
  25. Regulation and function of cGMP dependent protein kinase in cardiac hypertrophy
    Eiki Takimoto; Fiscal Year: 2013
    ..inducible conditional) and animals harboring mutant cGKI1 in which critical protein- protein interaction site (leucine zipper motif) is disrupted...
  26. NLR Family Proteins: Mechanisms and Regulation
    John C Reed; Fiscal Year: 2012
    ..NLRs contain a nucleotide-binding fold called NACHT, plus variable numbers of Leucine-Rich Repeat (LRR) domains, often combined with either PYRIN domains (PYDs) or Caspase-associated recruitment ..
  27. Mechanism of Apoptosis and Inhibition of Tumor Progression and Metastasis by Par-
    Vivek M Rangnekar; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Prostate apoptosis response-4 protein (Par-4;also known as PAWR) is a leucine zipper domain protein that is conserved in vertebrates...
  28. mt-Nd2 and Resistance to Autoimmune Diabetes
    Clayton E Mathews; Fiscal Year: 2011
    ..are not commonly associated with autoimmune Type 1 diabetes (T1D), although a C to A transversion resulting in a leucine to methonine substitution in the mt-ND2 gene has been associated with protection from T1D in both an at risk ..
  29. Regulation of Muscle ATP Synthase Beta Subunit Metabolism in Obesity
    Christos S Katsanos; Fiscal Year: 2013
    ..which is the main end-point of this proposal, will be determined using an intravenous constant infusion of d9-leucine in obese and non-obese subjects, and by measuring the d9-leucine enrichment of a [unreadable] -F1-ATPase peptide...
  30. Tannerella forsythia intercations with host cells and other bacteria
    Ashu Sharma; Fiscal Year: 2012
    ..forsythia. The BspA protein belongs to the leucine-rich-repeat as well as to the bacterial immunoglobulin-like superfamilies of proteins...
  31. Defining the Role of MafA in Islet Beta Cells
    Roland W Stein; Fiscal Year: 2013
    ..Our analyses of MafA and MafB protein chimeras have shown that the C-terminal leucine- zipper (dimerization) region regulates the distinct endogenous insulin gene activation ability of MafA in cell-..
  32. Atypical Antipsychotics: Effects on Hepatic Glucose and Lipid Metabolism in Human
    Michael R Rickels; Fiscal Year: 2012
    ..subjects will undergo an 17-h infusion of [1-13C] labeled acetate and 15-h infusion of [5,5,5,-2H3] labeled leucine to determine hepatic de novo lipogenesis and VLDL apobB100 production prior to and following administration of ..
  33. Oxidative activation of Src in smoke-induced epithelial mesenchymal transition
    Henry Jay Forman; Fiscal Year: 2013
    ..Cysteine residues identified in Aim 1 will b mutated individually or in pairs to leucine to mimic alkylation and the mutated plasmid will be expressed in cells...
  34. Enhancement of Medullary Erythropoiesis during Anemia by Trib3
    David Kuhrt; Fiscal Year: 2013
    ..Here I will assess Trib3's roles as an effector of the unfolded protein response as induced by leucine or glucose limitation, and during sustained EPO administration...
  35. Regulation of Transcriptional Activity of Hypoxia Inducible Factor 2
    Cheng Jun Hu; Fiscal Year: 2012
    ..The specific objective of this application is to characterize the role of the basic-helix-loop-helix-leucine zipper transcription factor, upstream stimulatory factor 2 (USF2) in regulating HIF2( transcriptional activity...
  36. AP-1 Complexes and Target Gene Regulation
    Elizabeth J Taparowsky; Fiscal Year: 2010
    ..AP-1 is a widely expressed transcription complex consisting of dimerizing basic leucine zipper (bZIP) proteins...
  37. Conformational Changes Underlying Intracellular Gating of the Leucine Transporter
    Kelli Kazmier; Fiscal Year: 2012
    ..Investigations in this proposal will focus on the leucine transporter (LeuT), a bacterial member of the NSS family and the preeminent model for understanding NSS function...
    Sean J Morrison; Fiscal Year: 2013
    ..We discovered that Leucine-rich glioma inactivated gene-4 (Lgi4), which encodes a secreted protein, was much more highly expressed in NCSCs...
  39. Benefits of dietary essential amino acid restriction
    James Mitchell; Fiscal Year: 2013
    ..Importantly, we have also found that restriction of two other essential amino acids - tryptophan and leucine - lend similar benefits...
  40. Regulation and Function of C/EBP in UVB Responses
    Robert C Smart; Fiscal Year: 2010
    The basic leucine zipper (bZIP) transcription factor, CCAAT/enhancer binding protein-a/(C/EBPa) is abundantly expressed within keratinocytes of the epidermis, however relatively little is known regarding its function in skin...
  41. Genotoxic NF-kB Signaling in Cancer
    Zhaohui Wu; Fiscal Year: 2013
    ..We found ELKS (a protein rich in glutamate, leucine, lysine and serine) is indispensable for the activation of IKK complex and NF-kappaB by genotoxic agents...
  42. Biogenic Amine Transporters: Mechanisms of Ligand Interaction
    MAARTEN E REITH; Fiscal Year: 2013
    ..Structural insight into these proteins has recently come from crystallization of a bacterial homolog, the leucine transporter LeuT, showing the location of the substrate binding site (termed S1 in the following), a region with ..
  43. Nrf2 signaling and oxidative stress in Age-related macular degeneration
    James T Handa; Fiscal Year: 2013
    ..Nuclear factor- erythroid 2-related factor 2 (Nrf2), a basic leucine zipper redox-sensitive transcription factor, regulates the inducible expression of antioxidant and cytoprotective ..
  44. Critical Role of Nrf2 in Innate Immune Response and Survival During Sepsis
    Shyam Biswal; Fiscal Year: 2010
    ..Nrf2 is a basic leucine zipper transcription factor that regulates the expression of antioxidant genes including the glutathione pathway ..
  45. Nlrp3 inflammasome signaling in immune responses to Candida albicans
    Fayyaz S Sutterwala; Fiscal Year: 2013
    ..albicans are required. In this proposal we will examine the role of the nucleotide-binding domain leucine-rich repeat containing receptor (NLR) family member Nlrp3 in recognition and response to infection with C...
  46. Elucidating Protein Folding Mechanisms
    Jay R Winkler; Fiscal Year: 2010
    ..Work on Aim 3 involves placement of fluorinated leucine, isoleucine, and valine residues at selected locations in four-helix-bundle proteins with the aim of optimizing ..
  47. The Role of Biglycan in Reproduction
    ..In the mouse model, defects in the expression of biglycan, an extracellular matrix small leucine-rich proteoglycan that is highly expressed in gestational tissues, are associated with an Ehlers-Danlos syndrome-..
  48. Amino Acid Regulation of Alternative Splicing
    Michael S Kilberg; Fiscal Year: 2013
    ..Two of these isoforms, full- length ATF3 (ATF3-FL) and a form with a truncated leucine zipper, ATF3?Zip3, are induced in expression by low protein diet in vivo or by amino acid deprivation of cultured ..
  49. polr1c and polr1d mutant zebrafish as new models for Treacher Collins syndrome
    KRISTIN EMILY NOACK WATT; Fiscal Year: 2013
    ..We hypothesize that dietary leucine will stimulate ribosome biogenesis and proliferation while reducing neuroepithelial cell death, restoring the NC ..
  50. Factors influencing regulation of the dynamics of the actin filament pointed end
    Alla S Kostyukova; Fiscal Year: 2013
    ..Aim 2 tests the hypothesis: The Leucine-Rich- Repeat (LRR) domain in Tmod binds factors that regulate its function...
    JUAN L BRUSES; Fiscal Year: 2011
    ..This analysis led to the identification of a group of proteins containing immunoglobulin (Ig) domains, leucine-rich repeats (LRR), or other protein interacting domains that are substantially up-regulated during the ..
  52. Novel Type 2 Diabetes Mellitus Preventive Therapies
    Carine M Lenders; Fiscal Year: 2010
    ..Given the emerging evidence that glutamine and leucine (building blocks of protein) may affect energy partition and thus diabetes risk, and that the relationship of ..
  53. Signaling Mechanisms in Plant Innate Immunity
    Jen Sheen; Fiscal Year: 2012
    ..Recent discoveries have revealed remarkable convergent evolution in the recognition of diverse MAMPs by leucine-rich-repeat receptors and the activation of multiple MAPK cascades in plants, animals and humans...
  54. AKAP Regulation of Neuronal L-type Calcium Channel Signaling to the Nucleus
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ..2 through a modified leucine zipper (LZ) motif and anchors the cAMP-dependent protein kinase (PKA) and Ca2+-calmodulin (CaM)-activated protein ..
  55. Synaptic target selection in Drosophila
    KAI G ZINN; Fiscal Year: 2013
    ..Six of the genes are in a specific family encoding proteins with extracellular domains containing leucine-rich repeats (LRRs), which are protein interaction modules...
  56. Dual Function of VPO1 in Pathogen Recognition and Killing
    Guangjie Cheng; Fiscal Year: 2013
    ..hPx family in that it contains a catalytic domain at its C-terminus and a large N-terminal region including five leucine-rich regions (LRRs) and four immunoglobulin (Ig) C2 type domains...
  57. Single molecule measurements on von Willebrand factor A1 and A2 domains
    Timothy A Springer; Fiscal Year: 2013
    ..ReaLISM is a fusion protein that consists from N to C- terminus of the A1 domain, a polypeptide linker, and the leucine-rich repeat domain of GPIb1...
  58. rAAV5-hCNGB3 Gene Therapy for Achromatopsia: Safety and Efficacy in a Dog Model
    Guo jie Ye; Fiscal Year: 2013
    ..related to a presumed cryptic promoter, we will also introduce a mutation at codon 340 (from methionine to leucine), and additional silent mutations (i.e...
  59. Interplay of Innate and Adaptive Immunity in Lupus Pathogenesis
    Michelle L Hermiston; Fiscal Year: 2013
    ..Molecular modeling of the TLR9 polymorphisms indicate they map to leucine rich repeats in the DNA ligand binding domain...
  60. Cellular Targets of Polyomavirus Tumor Antigens
    David C Pallas; Fiscal Year: 2012
    ..Reversible methylation of the PP2A catalytic subunit by Leucine Carboxy Methyltransferase (LCMT-1) and Protein Methylesterase-1 (PME-1) is the most specific cellular mechanism ..
  61. Mechanisms of retinal angiogenesis
    Gadiparthi N Rao; Fiscal Year: 2013
    ..CREB belongs to a basic/leucine zipper (bZIP) family of transcriptional factors and possess the ability to bind o the consensus sequence TGAC/..
  62. Impact of CR on inflammasome driven immune-metabolic interactions.
    Vishwa Deep Dixit; Fiscal Year: 2013
    ..The protein-protein interactions between Nlrp3 (for nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing-3), the adaptor protein Asc, and procaspase1 lead to the ..
    VINCENT CHIAPPINELLI; Fiscal Year: 1992
    ..Substance P-like and leucine-enkephalin-like immunoreactivities have been localized within dense core vesicles in a majority of the ..
    Brendan Lee; Fiscal Year: 2006
    ..We argue therefore that because of the importance of leucine to protein metabolic regulation, treatment with phenyl butyrate not only diverts N away from urea synthesis, but ..
    David Low; Fiscal Year: 2006
    ..by applicant): The goal of this proposal is to understand the mechanisms by which DNA adenine methylase (DAM), leucine-responsive regulatory protein (Lrp), and PapI orchestrate the reversible switch between OFF and ON Pap pili ..
  66. Poly (amino acid) as an Integrin Targeted Drug Carrier
    Xiaoling Li; Fiscal Year: 2005
    ..It is reported that the recognition of the tripeptide sequence, leucine-aspartic acid-valine, (LDV) is limited only to the a4a1 integrin...
  67. Immune Recovery Following LLME Treated Cell Therapy
    Joanne Filicko; Fiscal Year: 2006
    ..unreadable] [unreadable] GVHD appears to be mediated by T cells bearing cytotoxic effector granules. L-Leucyl-L-Leucine Methyl Ester (LLME) is polymerized by one of the enzymes within cytotoxic granules, resulting in the destruction ..
  68. Biological role of modifications to C/EBPbeta-1 and -2
    Linda Sealy; Fiscal Year: 2007
    The basic leucine zipper transcription factor, C/EBPbeta, is critical for growth and differentiation of the mammary gland...
    Thomas Gillis; Fiscal Year: 2003
    ..The TB vaccines are: 1) leucine auxotroph of BCG, 2) leucine auxotroph of MT, 3) MT culture filtrate in adjuvant prepared from the nontoxic ..