igf type 2 receptor

Summary

Summary: A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain.

Top Publications

  1. ncbi Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network
    K Karlsson
    Department of Medical Biochemistry and Biophysics, University of Umea, S 901 87 Umea, Sweden
    J Biol Chem 273:18966-73. 1998
  2. pmc Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor
    Cecilia N Arighi
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 165:123-33. 2004
  3. ncbi Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture
    L E Young
    Roslin Institute Edinburgh, Roslin, Midlothian, Scotland, UK
    Nat Genet 27:153-4. 2001
  4. ncbi TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking
    E Diaz
    Department of Biochemistry, Stanford University School of Medicine, California 94305 5307, USA
    Cell 93:433-43. 1998
  5. ncbi Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality
    M M Lau
    Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110
    Genes Dev 8:2953-63. 1994
  6. ncbi Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene
    Z Q Wang
    Research Institute for Molecular Pathology I M P, Vienna, Austria
    Nature 372:464-7. 1994
  7. pmc Mannose 6-phosphate receptors are sorted from immature secretory granules via adaptor protein AP-1, clathrin, and syntaxin 6-positive vesicles
    J Klumperman
    Department of Cell Biology and Center for Electron Microscopy, University of Utrecht, School of Medicine, 3584CX Utrecht, The Netherlands
    J Cell Biol 141:359-71. 1998
  8. ncbi Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary
    J K Killian
    Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA
    Hum Mol Genet 10:1721-8. 2001
  9. pmc Differences in the endosomal distributions of the two mannose 6-phosphate receptors
    J Klumperman
    Department of Cell Biology, Utrecht University, The Netherlands
    J Cell Biol 121:997-1010. 1993
  10. ncbi P-type lectins
    Nancy M Dahms
    Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Biochim Biophys Acta 1572:317-40. 2002

Detail Information

Publications235 found, 100 shown here

  1. ncbi Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network
    K Karlsson
    Department of Medical Biochemistry and Biophysics, University of Umea, S 901 87 Umea, Sweden
    J Biol Chem 273:18966-73. 1998
    ..The results indicate that membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs...
  2. pmc Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor
    Cecilia N Arighi
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 165:123-33. 2004
    ..These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN...
  3. ncbi Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture
    L E Young
    Roslin Institute Edinburgh, Roslin, Midlothian, Scotland, UK
    Nat Genet 27:153-4. 2001
    ..This highlights the potential benefits of epigenetic diagnostic screening in developing embryo procedures...
  4. ncbi TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking
    E Diaz
    Department of Biochemistry, Stanford University School of Medicine, California 94305 5307, USA
    Cell 93:433-43. 1998
    ..These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi...
  5. ncbi Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality
    M M Lau
    Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110
    Genes Dev 8:2953-63. 1994
    ..These results show that Igf2r is paternally imprinted and reveal that the receptor is crucial for regulating normal fetal growth, circulating levels of IGF2, and heart development...
  6. ncbi Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene
    Z Q Wang
    Research Institute for Molecular Pathology I M P, Vienna, Austria
    Nature 372:464-7. 1994
    ..A few (-/+) mice reactivated their paternal Igf2/Mpr allele in some tissues and survived to adults. But no (-/-) mice survived, indicating a role for the reactivated paternal allele in postnatal survival...
  7. pmc Mannose 6-phosphate receptors are sorted from immature secretory granules via adaptor protein AP-1, clathrin, and syntaxin 6-positive vesicles
    J Klumperman
    Department of Cell Biology and Center for Electron Microscopy, University of Utrecht, School of Medicine, 3584CX Utrecht, The Netherlands
    J Cell Biol 141:359-71. 1998
    ..Thus, we hypothesize that during secretory granule maturation, MPR-ligand complexes and syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then delivered to endosomes...
  8. ncbi Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary
    J K Killian
    Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA
    Hum Mol Genet 10:1721-8. 2001
    ..Moreover, the divergent evolution of M6P/IGF2R imprinting predicts that the success of in vitro embryo procedures such as cloning may be species dependent...
  9. pmc Differences in the endosomal distributions of the two mannose 6-phosphate receptors
    J Klumperman
    Department of Cell Biology, Utrecht University, The Netherlands
    J Cell Biol 121:997-1010. 1993
    ..These data suggest that the two MPRs exit the TGR via the same coated vesicles, but that upon arrival in the endosomes CD-MPR is more rapidly than CI-MPR, segregated into ATV which probably are destined to recycle MPRs to TGR...
  10. ncbi P-type lectins
    Nancy M Dahms
    Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Biochim Biophys Acta 1572:317-40. 2002
    ..This review provides a current view on the structures, functions, and medical relevance of the P-type lectins...
  11. ncbi M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity
    A T De Souza
    Department of Safety of Medicines, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK
    Nat Genet 11:447-9. 1995
    ..These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis...
  12. pmc Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes
    F Javier Pérez-Victoria
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 19:2350-62. 2008
    ..We also report that a Vps54 mutant protein in the Wobbler mouse strain is active in retrograde transport, thus explaining the viability of these mutant mice...
  13. ncbi Mannose 6-phosphate receptors: new twists in the tale
    Pradipta Ghosh
    Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Mol Cell Biol 4:202-12. 2003
    ..But trafficking of acid hydrolases is only part of the story. Evidence is emerging that one of the receptors can regulate cell growth and motility, and that it functions as a tumour suppressor...
  14. ncbi Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK
    T McKinnon
    Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 5C1
    J Clin Endocrinol Metab 86:3665-74. 2001
    ..We found that the extravillous trophoblast cells expressed an abundance of IGF type 2 receptor as detected by immunostaining and Western blots, and recombinant human IGF-II promoted their migration in a ..
  15. ncbi Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis
    B Motyka
    Department of Biochemistry, University of Alberta, Edmonton, Canada
    Cell 103:491-500. 2000
    ..These results suggest a novel target for immunotherapy and a potential mechanism used by tumors for immune evasion...
  16. pmc Mammalian GGAs act together to sort mannose 6-phosphate receptors
    Pradipta Ghosh
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 163:755-66. 2003
    ..The morphology of the TGN was also altered. These findings indicate that the three mammalian GGAs cooperate to sort cargo and are required for maintenance of TGN structure...
  17. ncbi Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting
    James Harper
    Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom
    Cancer Res 66:1940-8. 2006
    ..This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer...
  18. ncbi Trans-Golgi network syntaxin 10 functions distinctly from syntaxins 6 and 16
    Ya Wang
    Department of Biochemistry and Neurobiology Program, National University of Singapore, MD7, 8 Medical Drive, Singapore, 117597, Republic of Singapore
    Mol Membr Biol 22:313-25. 2005
    ....
  19. pmc Structure and functional analysis of the IGF-II/IGF2R interaction
    James Brown
    Cancer Research UK Receptor Structure Research Group, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK
    EMBO J 27:265-76. 2008
    ..Mutagenesis analyses confirm this IGF-II 'binding-hotspot', revealing that IGF-binding proteins and IGF2R have converged on the same high-affinity site...
  20. ncbi Proteomics analysis of serum from mutant mice reveals lysosomal proteins selectively transported by each of the two mannose 6-phosphate receptors
    Meiqian Qian
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Mol Cell Proteomics 7:58-70. 2008
    ..This study provides a comparison of different quantitative mass spectrometric approaches and provides the first report of proteins whose cellular targeting appears to be MPR-selective under physiological conditions...
  21. ncbi Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides
    Jez Carlton
    Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom
    Curr Biol 14:1791-800. 2004
    ..SNX1 is associated with early endosomes, from where it has been proposed to regulate the degradation of internalized epidermal growth factor (EGF) receptors through modulating endosomal-to-lysosomal sorting...
  22. ncbi Structural basis for recognition of acidic-cluster dileucine sequence by GGA1
    Tomoo Shiba
    Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization KEK, Tsukuba, Ibaraki 305 0801, Japan
    Nature 415:937-41. 2002
    ..This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein...
  23. ncbi Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids
    J X Kang
    Department of Medicine, Massachusetts General Hospital, Charlestown 02129 2000, USA
    Cell Growth Differ 10:591-600. 1999
    ....
  24. ncbi Insulin-like growth factors in human breast cancer
    M J Ellis
    Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
    Breast Cancer Res Treat 52:175-84. 1998
    ....
  25. ncbi Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds
    T Ludwig
    Department of Genetics and Development, Columbia University, New York, New York 10032, USA
    Dev Biol 177:517-35. 1996
    ....
  26. ncbi Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor
    B Schmidt
    Georg August Universitat, Zentrum für Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Gottingen, Federal Republic of Germany
    J Biol Chem 270:14975-82. 1995
    ..Residues 1508-1566, which are shared by the 23-kDa IGF-II-binding fragment and repeat 11, are proposed to form the IGF-II binding site of the M6P/IGF-II receptor...
  27. ncbi Loss of insulin-like growth factor II receptor expression promotes growth in cancer by increasing intracellular signaling from both IGF-I and insulin receptors
    C Osipo
    Division of Molecular and Cellular Biochemistry, Loyola University Medical Center, Maywood, Illinois 60153, USA
    Exp Cell Res 264:388-96. 2001
    ..The results directly demonstrate that down regulation of the IGF-IIR promotes the growth of transformed D9 cells by sustaining IGF-II, which binds to and activates IGF-IR and insulin receptor to increase intracellular growth signals...
  28. pmc Decreased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells
    Zhihong Chen
    Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
    BMC Cancer 2:18. 2002
    ..However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies...
  29. ncbi Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network
    Balraj Doray
    Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 297:1700-3. 2002
    ..MPRs that are defective in binding to GGAs are poorly incorporated into AP-1-containing clathrin-coated vesicles. Thus, the GGAs and AP-1 interact to package MPRs into AP-1-containing coated vesicles...
  30. ncbi The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells
    A Oshima
    E A Doisy Department of Biochemistry, St Louis University School of Medicine, Missouri 63104
    J Biol Chem 263:2553-62. 1988
    ....
  31. ncbi The GGA proteins: adaptors on the move
    Juan S Bonifacino
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T Room 101, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 5:23-32. 2004
    ....
  32. ncbi Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains
    H Takatsu
    Institute of Biological Sciences and Gene Experiment Center, University of Tsukuba, Tsukuba Science City, Ibaraki 305 8572, Japan
    J Biol Chem 276:28541-5. 2001
    ..These results indicate that GGA proteins regulate the localization to or exit from the TGN of the sorting receptors...
  33. ncbi The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans
    V M Kalscheuer
    Department of Human Genetics, University Hospital Nijmegen, The Netherlands
    Nat Genet 5:74-8. 1993
    ..The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome...
  34. ncbi Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor
    Y Zhu
    Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 292:1716-8. 2001
    ..The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting...
  35. ncbi Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains
    Saurav Misra
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 415:933-7. 2002
    ..The rigid spatial alignment of the three binding subsites leads to high specificity...
  36. ncbi M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan
    Yoshihiko Oka
    Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA
    Hepatology 35:1153-63. 2002
    ..Loss of heterozygosity in dysplastic liver nodules provides additional evidence that M6P/IGF2R haploid insufficiency is an early event in human hepatocarcinogenesis...
  37. ncbi Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins
    Balraj Doray
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:18477-82. 2002
    ..These studies provide an explanation for the observed differences in the relative affinities of the two MPRs for the GGA proteins. Furthermore, they indicate that the GGAs participate in lysosomal enzyme sorting mediated by the CD-MPR...
  38. ncbi Alternative mechanisms for trafficking of lysosomal enzymes in mannose 6-phosphate receptor-deficient mice are cell type-specific
    F Dittmer
    Georg August Universitat Gottingen, Abt Biochemie II, Gosslerstr 12 D, Germany
    J Cell Sci 112:1591-7. 1999
    ....
  39. ncbi Rescue of the T-associated maternal effect in mice carrying null mutations in Igf-2 and Igf2r, two reciprocally imprinted genes
    A J Filson
    Department of Genetics and Development, Columbia University, New York, NY 10032
    Development 118:731-6. 1993
    ..Based on these data, the Tme phenotype can be viewed as a dominant effect resulting from an overabundance of IGF-II...
  40. ncbi The insulin-like growth factor-II receptor gene is associated with type 1 diabetes: evidence of a maternal effect
    Jennifer A McCann
    Department of Pediatrics, McGill University Health Center Children s Hospital, 2300 Tupper, Suite C244, Montreal, Quebec, Canada H3H 1P3
    J Clin Endocrinol Metab 89:5700-6. 2004
    ..Thus, we present evidence that maternal alleles at an IGF2R polymorphism are associated with T1D. It is thus possible that at some tissue or developmental stage not yet examined, IGF2R is universally imprinted...
  41. ncbi Mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor. A consensus casein kinase II site followed by 2 leucines near the carboxyl terminus is important for intracellular targeting of lysosomal enzymes
    H J Chen
    Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854
    J Biol Chem 268:22338-46. 1993
    ....
  42. ncbi Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth
    K Kaku
    Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Chiba University Hospital, Chiba, Japan
    Acta Paediatr 96:363-7. 2007
    ..The aim of this study was to investigate the associations between the neonatal birth weight and the genotypes of polymorphic loci in the IGF2 and IGF2 receptor (IGF2R) genes...
  43. ncbi PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization
    L Wan
    Vollum Institute, The Oregon Health Sciences University, Portland 97201, USA
    Cell 94:205-16. 1998
    ..Cell-free assays indicate TGN localization of furin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian cells are localized to the TGN...
  44. ncbi Insulin-like growth factor II receptor as a multifunctional binding protein
    D O Morgan
    Nature 329:301-7. 1987
    ..The structural and biochemical features of the IGF-II receptor appear identical to those of the cation-independent mannose-6-phosphate receptor...
  45. ncbi Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal
    R Stöger
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 73:61-71. 1993
    ..These data suggest that the expressed locus carries a potential imprinting signal and imply that methylation is necessary for expression of the Igf2r gene...
  46. pmc PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic
    C M Crump
    Vollum Institute, L 474, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201 3098, USA
    EMBO J 20:2191-201. 2001
    ..These studies demonstrate the requirement for PACS-1 interactions with adaptor proteins in multiple processes, including secretory granule biogenesis and HIV-1 pathogenesis...
  47. pmc Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor
    J N Glickman
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 8:1041-7. 1989
    ..This signal is presumably responsible for the concentration of the M6P receptor, with bound lysosomal enzymes, into coated pits which bud from the trans-Golgi network, thus mediating efficient transfer of these enzymes to lysosomes...
  48. pmc A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking
    Gregory K Scott
    Vollum Institute, Oregon Health and Science University, Oregon Health Sciences University, Portland, 97239, USA
    EMBO J 25:4423-35. 2006
    ..Our results identify a CK2-controlled cascade regulating hydrolase trafficking and sorting of itinerant proteins in the TGN/endosomal system...
  49. pmc Visualization of TGN to endosome trafficking through fluorescently labeled MPR and AP-1 in living cells
    Satoshi Waguri
    Institut de Biologie, EP CNRS 525, Institut Pasteur de Lille, 59021 Lille Cedex, France
    Mol Biol Cell 14:142-55. 2003
    ....
  50. pmc Identification of residues in TIP47 essential for Rab9 binding
    John Hanna
    Department of Biochemistry, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305 5307, USA
    Proc Natl Acad Sci U S A 99:7450-4. 2002
    ..These experiments reveal distinct binding domains for the Rab9 GTPase and MPR cytoplasmic domains in the cargo selection protein TIP47...
  51. pmc mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors
    C Meyer
    Zentrum für Biochemie und Molekulare Zellbiologie, Dept Biochemie II, Universitat Gottingen, Heinrich Düker Weg 12, D 37073 Gottingen, Germany
    EMBO J 19:2193-203. 2000
    ..MPR46 fails to recycle back from the endosome to the TGN, indicating that AP-1 is required for retrograde endosome to TGN transport of the receptor...
  52. pmc Endocytosed cation-independent mannose 6-phosphate receptor traffics via the endocytic recycling compartment en route to the trans-Golgi network and a subpopulation of late endosomes
    Sharron X Lin
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Biol Cell 15:721-33. 2004
    ..These data demonstrate that CI-MPR takes a complex route that involves multiple sorting steps in both early and late endosomes...
  53. ncbi Mutations of transforming growth factor beta 1 type II receptor, BAX, and insulin-like growth factor II receptor genes in microsatellite unstable cell lines
    J M Carethers
    Department of Medicine and Cancer Center, University of California, San Diego, USA
    In Vivo 14:13-20. 2000
    ..In ovarian cancer cells with MSI, mutations in TGF beta RII, BAX, and IGFIIR may be unimportant in the genesis of this tumor...
  54. ncbi Receptor extracellular domains may contain trafficking information. Studies of the 300-kDa mannose 6-phosphate receptor
    S M Dintzis
    Department of Biochemistry, Stanford University School of Medicine, California 94305 5307
    J Biol Chem 269:12159-66. 1994
    ..These experiments suggest that the presence of the mannose 6-phosphate receptor extracellular domain may interfere with the rapid recycling of receptors from early endosomes to the cell surface and detain receptors within endosomes...
  55. ncbi The GGA proteins: key players in protein sorting at the trans-Golgi network
    Pradipta Ghosh
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Eur J Cell Biol 83:257-62. 2004
    ..This review covers the recent structural and cell biological studies that have provided mechanistic insights into the function of the GGAs in mannose 6-phosphate receptor trafficking...
  56. pmc Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur
    James Brown
    Cancer Research UK Receptor Structure Research Group, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK
    EMBO J 21:1054-62. 2002
    ..The structure factors and coordinates of IGF2R domain 11 have been deposited in the Protein Data Bank (accession codes 1GP0 and 1GP3)...
  57. ncbi Quantitative analysis of TIP47-receptor cytoplasmic domain interactions: implications for endosome-to-trans Golgi network trafficking
    J P Krise
    Department of Biochemistry, Stanford University School of Medicine, CA 94305 5307, USA
    J Biol Chem 275:25188-93. 2000
    ..Moreover, our data suggest unexpectedly that furin, TGN38, and carboxypeptidase D may use a distinct vesicular carrier and perhaps a distinct route for transport between endosomes and the trans Golgi network...
  58. ncbi TIP47 is not a component of lipid droplets
    P Barbero
    Department of Biochemistry, Stanford University School of Medicine, Stanford, California 95307, USA
    J Biol Chem 276:24348-51. 2001
    ..Using antibodies specific for residues 152-434 of TIP47, we show that TIP47 is not a constituent of lipid droplets...
  59. pmc Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells
    Pierre Barbero
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Cell Biol 156:511-8. 2002
    ..Our data suggest that Rab9 remains vesicle associated until docking with the Golgi complex and is rapidly removed concomitant with or just after membrane fusion...
  60. ncbi Role of Rab9 GTPase in facilitating receptor recruitment by TIP47
    K S Carroll
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305 5307, USA
    Science 292:1373-6. 2001
    ..Thus, a cytosolic cargo selection device may be selectively recruited onto a specific organelle, and vesicle budding might be coupled to the presence of an active Rab GTPase...
  61. ncbi The 3' UTR IGF2R-A2/B2 variant is associated with increased tumor growth and advanced stages in non-small cell lung cancer
    Athanassios Kotsinas
    Department of Histology and Embryology, Molecular Carcinogenesis Group, School of Medicine, University of Athens, Athens, Greece
    Cancer Lett 259:177-85. 2008
    ..In conclusion, the IGF2R-A2/B2 variant probably provides a selective advantage for NSCLC progression through increased tumor growth...
  62. pmc Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer
    Matthew N J Seaman
    Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust MRC Building, Addenbrookes Hospital, Hills Road, Cambridge CB2 2XY, England, UK
    J Cell Biol 165:111-22. 2004
    ..The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin...
  63. ncbi Clathrin adaptor epsinR is required for retrograde sorting on early endosomal membranes
    Agnes Saint-Pol
    Laboratoire Trafic et Signalisation, 75248 Paris Cedex 05, France
    Dev Cell 6:525-38. 2004
    ..In conclusion, our work reveals the existence of clathrin-independent and -dependent transport steps in the retrograde route, and establishes a function for clathrin and epsinR at the endosome-TGN interface...
  64. ncbi Interactions of GGA3 with the ubiquitin sorting machinery
    Rosa Puertollano
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Cell Biol 6:244-51. 2004
    ..The VHS and GAT domains of GGA3 are responsible for this binding, as well as for interactions with TSG101, a component of the ubiquitin-dependent sorting machinery. Thus, GGAs may have additional roles in sorting of ubiquitinated cargo...
  65. ncbi Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations
    J K Killian
    Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Hum Mutat 18:25-31. 2001
    ..Three identified amino-acid variants in the M6P/IGF2R ligand-binding domains may be under selection in humans...
  66. pmc Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein
    J G Orsel
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305 5307, USA
    Proc Natl Acad Sci U S A 97:9047-51. 2000
    ..Although crystallography will be needed to define the precise interaction interface, these data provide an initial structural basis for TIP47-CI-MPR association...
  67. ncbi Real time kinetics of insulin-like growth factor II (IGF-II) interaction with the IGF-II/mannose 6-phosphate receptor: the effects of domain 13 and pH
    J Linnell
    Department of Zoology, University of Oxford, South Parks Rd, Oxford, OX1 3PS, United Kingdom
    J Biol Chem 276:23986-91. 2001
    ..0-7.4. The constructs behaved differently in response to pH and in recovery after low pH exposure, suggesting that pH stability of the extracellular domains depends on domains other than 10-13...
  68. ncbi The human brain mannose 6-phosphate glycoproteome: a complex mixture composed of multiple isoforms of many soluble lysosomal proteins
    David E Sleat
    Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
    Proteomics 5:1520-32. 2005
    ..We found that the human brain Man6-P-containing lysosomal proteome is highly complex and contains more proteins with a much greater number of individual isoforms than found in previous studies of Man6-P glycoproteomes...
  69. pmc Cholesterol accumulation sequesters Rab9 and disrupts late endosome function in NPC1-deficient cells
    Ian G Ganley
    Department of Biochemistry, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305 5307, USA
    J Biol Chem 281:17890-9. 2006
    ..We conclude that cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor trafficking...
  70. pmc A novel Rab9 effector required for endosome-to-TGN transport
    E Diaz
    Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305 5307, USA
    J Cell Biol 138:283-90. 1997
    ..These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking...
  71. ncbi A novel assay reveals a role for soluble N-ethylmaleimide-sensitive fusion attachment protein in mannose 6-phosphate receptor transport from endosomes to the trans Golgi network
    C Itin
    Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305 5307, USA
    J Biol Chem 272:27737-44. 1997
    ..Together with alpha-SNAP, NSF can increase the extent of transport. These data show that alpha-SNAP, a soluble component of the SNAP receptor machinery, facilitates transport from endosomes to the trans Golgi network...
  72. ncbi Sorting of mannose 6-phosphate receptors mediated by the GGAs
    R Puertollano
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 292:1712-6. 2001
    ..A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network...
  73. pmc A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling
    Jonathan V Reddy
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305 5307, USA
    Mol Biol Cell 17:4353-63. 2006
    ..These data assign a specific pathway to an interesting, TGN-localized protein and suggest that GCC185 may participate in the docking of late endosome-derived, Rab9-bearing transport vesicles at the TGN...
  74. pmc Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors
    Raul Rojas
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T Room 101, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 27:1112-24. 2007
    ....
  75. ncbi Localization of the carbohydrate recognition sites of the insulin-like growth factor II/mannose 6-phosphate receptor to domains 3 and 9 of the extracytoplasmic region
    Michael K Hancock
    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Biol Chem 277:47205-12. 2002
    ....
  76. pmc Neither type of mannose 6-phosphate receptor is sufficient for targeting of lysosomal enzymes along intracellular routes
    D Kasper
    Georg August University, Abt Biochemie II, Gottingen, Germany
    J Cell Biol 134:615-23. 1996
    ..These results imply that neither overexpression of MPR 46 nor MPR 300 is sufficient for targeting of lysosomal proteins along intracellular routes...
  77. ncbi Insulin-like growth factor II receptor gene-167 genotype increases the risk of oral squamous cell carcinoma in humans
    Athanasios I Zavras
    Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA
    Cancer Res 63:296-7. 2003
    ..7, 95% confidence interval: 1.16-6.48), controlling for major confounders. Our results suggest that genetic variation of IGF2R may influence significantly the risk of oral cancer...
  78. ncbi Kinetics of insulin-like growth factor II (IGF-II) interaction with domain 11 of the human IGF-II/mannose 6-phosphate receptor: function of CD and AB loop solvent-exposed residues
    Oliver J Zaccheo
    Cancer Research UK Molecular Oncology and Growth Factor Research Group, Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    J Mol Biol 359:403-21. 2006
    ..These findings have implications for the molecular architecture and evolution of the domain 11 IGF-II-binding site, and the potential interactions with other domains of IGF2R...
  79. ncbi Structural insights into the interaction of insulin-like growth factor 2 with IGF2R domain 11
    Christopher Williams
    Department of Organic and Biological Chemistry, School of Chemistry, Cantock s Close, University of Bristol, Bristol, United Kingdom
    Structure 15:1065-78. 2007
    ..The models reveal that the molecular interaction is driven by critical hydrophobic residues on IGF2 and IGF2R, while a ring of flexible, charged residues on IGF2R may modulate binding...
  80. ncbi Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height
    Clive J Petry
    Department of Paediatrics, University of Cambridge, Box 116, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
    Growth Horm IGF Res 15:363-8. 2005
    ..We hypothesised that polymorphisms in the IGF2R gene could alter size at birth and childhood growth...
  81. ncbi The kangaroo cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II with low affinity
    C A Yandell
    Cooperative Research Centre for Tissue Growth and Repair, P O Box 10065, Adelaide B C, South Australia, Australia, 5000
    J Biol Chem 274:27076-82. 1999
    ..Thus, the acquisition of a high-affinity binding site for regulating IGF-II appears to be a recent event specific to the eutherian lineage...
  82. pmc Sorting nexin-2 is associated with tubular elements of the early endosome, but is not essential for retromer-mediated endosome-to-TGN transport
    Jez G Carlton
    Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
    J Cell Sci 118:4527-39. 2005
    ....
  83. ncbi Phosphoregulation of sorting signal-VHS domain interactions by a direct electrostatic mechanism
    Yukio Kato
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Struct Biol 9:532-6. 2002
    ....
  84. ncbi Domain interactions of the mannose 6-phosphate/insulin-like growth factor II receptor
    Jodi L Kreiling
    Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198 5870, USA
    J Biol Chem 280:21067-77. 2005
    ..We conclude that there is no finite M6P/IGF2R dimerization domain, but rather that interactions between dimer partners occur all along the extracytoplasmic region of the receptor...
  85. ncbi Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in mice
    A Wutz
    Research Institute for Molecular Pathology IMP, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Development 128:1881-7. 2001
    ..These data show that the biological function of imprinting Igf2r is to increase birth weight and they also establish Igf2r as the Tme gene...
  86. pmc The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin
    Stephane Lefrancois
    Department of Anatomy and Cell Biology, McGill University, 3640 University Montreal, Quebec, Canada H3A 2B2
    EMBO J 22:6430-7. 2003
    ..In conclusion, our results show that the trafficking of SAPs is dependent on sortilin, demonstrating a novel lysosomal trafficking...
  87. pmc Cloning of the bovine 215-kDa cation-independent mannose 6-phosphate receptor
    P Lobel
    Proc Natl Acad Sci U S A 84:2233-7. 1987
    ..Each repeat contains a highly conserved 13-amino acid unit bordered by cysteine residues that may be functionally important...
  88. ncbi Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells
    Ho Seong Kim
    Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA
    Cancer Res 64:2229-37. 2004
    ....
  89. ncbi Cell proliferation and migration in glioblastoma multiforme cell lines are influenced by insulin-like growth factor I in vitro
    Anke Schlenska-Lange
    Hospital for Children and Adolescents, University of Leipzig, Liebigstr 20 a, D 04103 Leipzig, Germany
    Anticancer Res 28:1055-60. 2008
    ..In this study we investigated the expression of different members of the IGF system in malignant glioma cells and the influence of IGF-I and -II on the proliferation and migration of human glioma cell lines in vitro...
  90. ncbi Increased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivo
    Jason S Lee
    Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, St Leonards, NSW, Australia
    Int J Cancer 107:564-70. 2003
    ..These results therefore suggest that M6P/IGF-IIR levels can modulate breast cancer cell tumorigenicity by a mechanism that may involve altered IGF-I receptor signaling...
  91. ncbi IFN-gamma-mediated extravillous trophoblast outgrowth inhibition in first trimester explant culture: a role for insulin-like growth factors
    Yuxiang Hu
    Department of Obstetrics and Gynaecology, University of British Columbia, 2H30 4500 Oak Street, Vancouver, BC, Canada
    Mol Hum Reprod 14:281-9. 2008
    ..The observed IFN-gamma-mediated EVT migration inhibition may occur through the down-regulation of IGFR-2 and subtle induction of EVT apoptosis...
  92. ncbi Abundance of message for insulin-like growth factors-I and -II and for receptors for growth hormone, insulin-like growth factors-I and -II, and insulin in the intestine and liver of pre- and full-term calves
    T M Georgieva
    Division of Nutrition and Physiology, Institute of Animal Genetics, Nutrition and Housing, Faculty of Veterinary Medicine, University of Berne, CH 3012 Berne, Switzerland
    J Anim Sci 81:2294-300. 2003
    ..In conclusion, mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin were different at different intestinal sites and in intestine and liver and changed during the perinatal period...
  93. ncbi Role of the IGF-II receptor in mediating acute, non-genomic effects of retinoids and IGF-II on keratinocyte cell death
    F Louafi
    Division of Surgery, Bristol Royal Infirmary, Bristol, United Kingdom
    Exp Dermatol 12:426-34. 2003
    ..The inhibition of RA action by IGF-II was independent of its ability to signal through the IGF-I receptor or to interact with IGFBPs...
  94. ncbi Amino- and carboxyl-terminal fragments of insulin-like growth factor (IGF) binding protein-3 cooperate to bind IGFs with high affinity and inhibit IGF receptor interactions
    Louis D Payet
    Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia
    Endocrinology 144:2797-806. 2003
    ..This study demonstrates that isolated amino-terminal and carboxyl-terminal domains of IGFBP-3 cooperate in the presence of IGFs to form high-affinity complexes that retain the ability to block IGF activity...
  95. ncbi Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep
    Jaime A Duffield
    Discipline of Physiology, School of Molecular and Biomedical Sciences, The University of Adelaide, SA, Australia
    Am J Physiol Regul Integr Comp Physiol 294:R1413-9. 2008
    ....
  96. ncbi Affinity modulation of human placental insulin and insulin-like growth factor receptors by lectins
    Romana Masnikosa
    INEP Institute for the Application of Nuclear Energy, University of Belgrade, Banatska 31 B, 11080 Belgrade, 381 Serbia
    J Biochem 143:813-20. 2008
    ..The existence of modulators that would selectively inhibit or enhance the binding of IGFs or insulin to their corresponding receptors may have important implications for placental cell responses to these molecules...
  97. ncbi The insulin-like growth factor system in advanced breast cancer
    Svein Inge Helle
    Department of Oncology, Haukeland University Hospital, N 5021 Bergen, Norway
    Best Pract Res Clin Endocrinol Metab 18:67-79. 2004
    ....
  98. ncbi The insulin-like growth factor system and cancer
    Derek LeRoith
    Diabetes Branch, Room 8D12, Building 10, National Institutes of Health MSC 1758, Bethesda, MD 20892 1758, USA
    Cancer Lett 195:127-37. 2003
    ..In this review, many aspects of the IGF system and its relationship to cancer will be discussed...
  99. ncbi Developmental changes and the impact of isoflavones on mRNA expression of IGF-I receptor, EGF receptor and related growth factors in porcine skeletal muscle cell cultures
    Claudia Kalbe
    Research Institute for the Biology of Farm Animals, Research Unit Muscle Biology and Growth, Wilhelm Stahl Allee 2, Dummerstorf, Germany
    Growth Horm IGF Res 18:424-33. 2008
    ....
  100. ncbi Distinct actions of insulin-like growth factors (IGFs) on placental development and fetal growth: lessons from mice and guinea pigs
    C T Roberts
    Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, S A 5005, Australia
    Placenta 29:S42-7. 2008
    ..IGF-II within the fetus may also signal its nutrient demands to the placenta to improve its function to suit. Therefore each IGF of endocrine and local origin has important, but distinct, roles in placental development and function...
  101. ncbi Autocrine growth factor signaling by insulin-like growth factor-II mediates MyoD-stimulated myocyte maturation
    Elizabeth M Wilson
    Molecular Medicine Division, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    J Biol Chem 278:41109-13. 2003
    ..Our observations identify a robust autocrine amplification network in which MyoD enhances the later steps in muscle differentiation by induction of a locally acting growth factor...

Research Grants48

  1. Control of Breathing and Pompe Disease
    David D Fuller; Fiscal Year: 2013
    ..This renewal application targets optimization of adeno-associated virus (AAV) based therapies to treat respiratory neurons in Pompe disease. ..
  2. STRUCTURAL ANALYSIS OF THE MANNOSE 6-PHOSPHATE RECEPTORS
    Nancy M Dahms; Fiscal Year: 2013
    ..These studies will also provide the structural basis for the design of improved therapeutics for the treatment of lysosomal storage disorders, and novel inhibitors of viral infection and growth factor activation. ..
  3. Glycosylation-independent enzyme therapy of the brain in Sanfilippo B syndrome
    Patricia I Dickson; Fiscal Year: 2013
    ..abstract_text> ..
  4. Chlamydia Pneumoniae Antigens of Bilogogical Significance
    Lee Ann Campbell; Fiscal Year: 2012
    ..If this organism contributes to the pathology of cardiovascular disease, identification of targets for intervention or prevention is of paramount importance to public health. ..
  5. Phase 1/2 Study of Clenbuterol for the Treatment of Pompe Disease
    Dwight D Koeberl; Fiscal Year: 2013
    ..The study will be conducted at Duke University Hospital System with the review of the Duke Institutional Review Board under an investigator initiated IND. ..
  6. HUMAN PHAGOCYTES, OXYGEN METABOLITES AND INFLAMMATION
    Stephen Weiss; Fiscal Year: 2002
    ....
  7. Roles of Retromer Complex in Development
    Xinhua Lin; Fiscal Year: 2013
    ..Defects in Wnt and Toll signaling pathways as well as epithelium polarity are associated with many human diseases including cancers. The outcomes of this application will help understanding related human disease processes. ..
  8. ETHANOL EFFECTS ON PROTEOLYTIC SYSTEMS IN THE LIVER
    TERRENCE DONOHUE; Fiscal Year: 2003
    ..Specific Aims 3 and 4 will address third hypothesis by testing the capacity of hepatocytes and their extracts to degrade altered (i.e. aldehyde-modified) and native forms of lysozyme. ..
  9. IMPRINTING EVOLUTION AND CANCER SUSCEPTIBILITY
    Randy Jirtle; Fiscal Year: 2004
    ..The proposed studies will determine if mammalian cancer susceptibility is a detrimental result of genomic imprinting evolution. ..
  10. GLYCOPROTEIN SYNTHESIS, SECRETION, AND ENDOCYTOSIS
    MARTIN SNIDER; Fiscal Year: 1990
    ..Our experiments on asparagine-linked oligosaccharide assembly should make this the first system for which molecular and mechanistic details of this movement are understood...
  11. MICROSATELLITE INSTABILITY AND COLONIC NEOPLASIA IN IBD
    Amy Noffsinger; Fiscal Year: 2003
    ....
  12. Omega-6/Omega-3 Fatty Acid Ratio and Tumorigenesis
    Jing Kang; Fiscal Year: 2009
    ..Information derived from these studies will increase our understanding of the importance of n-3 fatty acids as well as n-6/n-3 fatty acid ratio in cancer prevention and help guide dietary advice. ..
  13. RETINOIDS, M6P/IGF II RECEPTOR & CELL GROWTH REGULATION
    Jing Kang; Fiscal Year: 2002
    ..This knowledge may lead to novel or more effective therapeutic and preventive approaches for cancer and developmental defects. ..
  14. Mechanisms for immune tolerance in Pompe Disease
    Dwight D Koeberl; Fiscal Year: 2010
    ..These comparisons will guide preclinical experiments to further immunomodulatory gene therapy in Pompe disease and other lysosomal storage disorders. ..
  15. Gene delivery to striated muscle by systemic AAV vectors
    Dwight D Koeberl; Fiscal Year: 2010
    ..Efficacious muscle-targeted gene therapy in GSD-II will have implications for gene therapy in other muscular dystrophies and myopathies. ..
  16. AASK NIH Cohort Study
    Joel Kopple; Fiscal Year: 2007
    ..Such results might eventually lead to new strategies that delay or prevent ESRD__ ..
  17. MEVALONATED METABOLIZING ENZYMES & THEIR INBORN DEFECTS
    Jung Ja Kim; Fiscal Year: 2003
    ..3) High resolution structures of rat and human mevalonate kinases will be determined by X-ray crystallography. (4) Human mevalonate kinase mutants will be modeled to determine the molecular basis for mevalonic aciduria. ..
  18. Muller glia and neuronal regeneration in the retina
    Andy Fischer; Fiscal Year: 2009
    ..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..
  19. CELL BIOLOGY OF CARBOXYPEPTIDASE D
    Lloyd Fricker; Fiscal Year: 2003
    ..This will provide a better understanding of the proteins, either known or novel, that interact with CPD. These studies on CPD will advance our knowledge of protein trafficking in neuroendocrine cells. ..
  20. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2010
    ..Aim 3 will use nuclear transplantation as a criterion to define the genetic and epigenetic alterations of the cancer cell genome that interfere with reversion to pluripotency. ..
  21. Molecular Analysis of the CCC185 Golgin
    Suzanne R Pfeffer; Fiscal Year: 2010
    ..This work has broad implications for our understanding of vesicle docking and fusion events within the secretory and endocytic pathways that are essential for normal human health and disease. ..
  22. Imprinted PEG3 domain at 19q13.4 and carcinogenesis
    Susan Murphy; Fiscal Year: 2002
    ..These studies will help clarify the role of the human PEG3 isoforms in the control of cellular growth, and may further contribute potential diagnostic and therapeutic targets for ovarian cancer. ..
  23. Development of the enteric nervous system: Cells & genes
    Michael Gershon; Fiscal Year: 2006
    ..The invited speakers include all of the leading researchers in the field, including Professor Nicole Le Douarin. We also anticipate that many post-graduate students and post-doctoral fellows will also attend. [unreadable] [unreadable]..
  24. PRODUCTION OF BETA-GLUCURONIDASE FOR MPS VII
    Emil Kakkis; Fiscal Year: 2002
    ..PROPOSED COMMERCIAL APPLICATION: The enzyme and process created from this work can be used to produce enzyme and treat patients suffering from Mucopolysaccharidosis VII, a serious, life-threatening genetic disorder. ..
  25. GENE DEFECTIVE IN HEREDITARY HEMOCHROMATOSIS
    William Sly; Fiscal Year: 2002
    ..These studies will not only improve our understanding of how iron absorption is normally regulated, but may also suggest new strategies for treating disorders of excessive iron absorption. ..
  26. REGULATION OF NEUROPEPTIDE PROCESSING ENZYMES
    Lloyd Fricker; Fiscal Year: 2002
    ..The results of these studies will provide a better understanding of the enzymes involved with peptide biosynthesis. ..
  27. LOCALIZATION OF THE GOLGI COMPLEX
    Suzanne Pfeffer; Fiscal Year: 2001
    ....
  28. MEMBRANE MECHANISMS MEDIATING ALCOHOL INDUCED PATHOLOGY
    Richard Gross; Fiscal Year: 2001
    ..Collectively, the proposed research represents a multidisciplinary approach designed to dissect the biochemical mechanisms underlying these novel effects of ethanol and ethanol metabolites on hippocampal function. ..
  29. Animal Models of Mucopolysaccharidosis
    Mark Haskins; Fiscal Year: 2008
    ..These animal studies are designed to facilitate our understanding of disease pathogenesis and the development of therapy for the neuronopathic and non-neuronopathic forms of MPS. ..
  30. In Vitro Reprogramming of Somatic Cells into Pluripotent ES-like Cells
    Rudolf Jaenisch; Fiscal Year: 2008
    ....
  31. Quantitative Peptidomics of Food Deprivation
    Lloyd Fricker; Fiscal Year: 2005
    ..The studies in this initial R21 will provide an unbiased survey of neuropeptides that are altered by food deprivation, and which may therefore be involved in regulating food intake and/or body weight. ..
  32. Peptidomics of Cocaine and Amphetamine Abuse
    Lloyd Fricker; Fiscal Year: 2005
    ..Taken together, these studies will provide a better understanding of the regulation of neuropeptides, both known and novel, in drug abuse. ..
  33. Structure/Mechanism of an FMN- and FAD-containing Enzyme
    Jung Ja Kim; Fiscal Year: 2005
    ..To determine the structural basis for these differences, it is proposed to determine the crystal structures of (4) the flavin domains and (5) their variants of the three NOSs, containing their respective Ca++/CaM-binding regions. ..
  34. SIMPLE VERTEBRATE AND INVERTEBRATE SYSTEMS
    Michael Gershon; Fiscal Year: 2005
    ..Almost all trainees have continued to be productive in biomedical science and some have acquired leadership positions. ..
  35. Paracrine Regulation of IGF-I in the Developing Ileum
    Phillip Gordon; Fiscal Year: 2006
    ..abstract_text> ..
  36. Molecular Dissection of IGF2R Growth Suppressor Activity
    Richard MacDonald; Fiscal Year: 2004
    ..These studies will contribute to understanding the receptor's tumor suppressor function and permit rational design of strategies that exploit the IGF2R in cancer prevention and therapy. ..
  37. Role of Chlamydia Pneumoniae in Atherosclerosis
    Cho Chou Kuo; Fiscal Year: 2007
    ..pneumoniae infection and reduction of atherosclerosis and coronary heart disease. ..
  38. BIOCHEMICAL GENETICS OF CARBONIC ANHYDRASE DEFICIENCIES
    William Sly; Fiscal Year: 2008
    ..The answers sought have fundamental significance, and should provide information leading to novel therapeutic approaches to CA deficiency. ..
  39. GENOMIC IMPRINTING AND THE CLONING OF MICE
    Rudolf Jaenisch; Fiscal Year: 2008
    ..This program attempts to define the biological parameters which limit the nuclear cloning approach. ..
  40. Function of Carboxypeptidase D
    Lloyd Fricker; Fiscal Year: 2008
    ..The overall goal of this proposal is to understand the role of each domain within CPD, using a simple organism for which CPD mutants exist and which is amenable to transgenic analysis. ..
  41. MECHANISMS OF GENOMIC IMPRINTING
    Andrew Hoffman; Fiscal Year: 2007
    ..Ultimately, it will be possible to develop a comprehensive chromatin/DNA model of imprinting. [unreadable] [unreadable]..
  42. PHOSPHOLIPASE ACTIVATION AND MEMBRANE DYSFUNCTION IN DIABETIC CARDIOMYOPATHY
    Richard Gross; Fiscal Year: 2008
    ..More specifically, the proposed studies identify the chemical changes in hearts of diabetic patients that lead to altered heart function and ultimately to heart failure. [unreadable] [unreadable] [unreadable]..
  43. INTRACELLULAR TRANSPORT--THE MANNOSE-PHOSPHATE RECEPTOR
    Suzanne Pfeffer; Fiscal Year: 2008
    ..These studies have important implications for our understanding of growth control and antigen processing, and will provide fundamental information regarding the mechanism of receptor trafficking in mammalian cells. ..
  44. Molecular Target(s) for Interruption of HBV Infection
    Jisu Li; Fiscal Year: 2009
    ..We hope these studies will contribute to the understanding of the early events of hepadnavirus infection and may lead to the development of novel antiviral strategies for prevention of HBV induced liver cancer. ..