The chemistry and biology of mucin-type O-linked glycosylation.

Mucin-type O-linked glycosylation is a fundamental post-translational modification that is involved in a variety of important biological processes. However, the lack of chemical tools to study mucin-type O-linked glycosylation has hindered our molecular understanding of O-linked glycans in many biological contexts. The review discusses the significance of mucin-type O-linked glycosylation initiated by the polypeptide N-acetylgalactosaminyltransferases in biology and development of chemical tools to study these enzymes and their substrates.

[1]  S. Withers,et al.  Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate , 2001, Nature.

[2]  Søren Brunak,et al.  O-GLYCBASE version 4.0: a revised database of O-glycosylated proteins , 1999, Nucleic Acids Res..

[3]  P. W. Kent,et al.  Polypeptide N-acetylgalactosaminyltransferase activity in tracheal epithelial microsomes. , 1992, The Biochemical journal.

[4]  R Apweiler,et al.  On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. , 1999, Biochimica et biophysica acta.

[5]  K. G. Hagen,et al.  A UDP-GalNAc:PolypeptideN-Acetylgalactosaminyltransferase Is Essential for Viability in Drosophila melanogaster * , 2002, The Journal of Biological Chemistry.

[6]  J. Esko,et al.  A disaccharide precursor of sialyl Lewis X inhibits metastatic potential of tumor cells. , 2003, Cancer research.

[7]  G. K. Hirst THE QUANTITATIVE DETERMINATION OF INFLUENZA VIRUS AND ANTIBODIES BY MEANS OF RED CELL AGGLUTINATION , 1942, The Journal of experimental medicine.

[8]  H. Nakada,et al.  Glycosylation of the tandem repeat unit of the MUC2 polypeptide leading to the synthesis of the Tn antigen. , 1998, Biochemical and biophysical research communications.

[9]  L. Tabak,et al.  Characterization of a UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase That Displays Glycopeptide N-Acetylgalactosaminyltransferase Activity* , 1999, The Journal of Biological Chemistry.

[10]  M. Hollingsworth,et al.  Substrate Specificities of Three Members of the Human UDP-N-Acetyl-α-d-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase Family, GalNAc-T1, -T2, and -T3* , 1997, The Journal of Biological Chemistry.

[11]  R. Cummings,et al.  Model Glycosulfopeptides from P-selectin Glycoprotein Ligand-1 Require Tyrosine Sulfation and a Core 2-branched O-Glycan to Bind to L-selectin* , 2003, Journal of Biological Chemistry.

[12]  M. Hollingsworth,et al.  Structural analysis of peptide substrates for mucin-type O-glycosylation. , 1998, Biochemistry.

[13]  M. Miles,et al.  Atomic force microscopy of the submolecular architecture of hydrated ocular mucins. , 1999, Biophysical journal.

[14]  J. van den Born,et al.  Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2. , 2003, Glycobiology.

[15]  J. Vliegenthart,et al.  Glycoproteins and disease , 1996 .

[16]  H. Takano,et al.  Structural basis for the regulation of UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 gene expression in adenocarcinoma cells. , 1999, Cancer research.

[17]  M. Meldal,et al.  Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Weiss,et al.  Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms , 2002, Nature Immunology.

[19]  Stephen G. Withers,et al.  Crystal structure of the retaining galactosyltransferase LgtC from Neisseria meningitidis in complex with donor and acceptor sugar analogs , 2001, Nature Structural Biology.

[20]  F. Real,et al.  GalNAc-α-O-benzyl Inhibits Sialylation ofde Novo Synthesized Apical but Not Basolateral Sialoglycoproteins and Blocks Lysosomal Enzyme Processing in a Post-trans-Golgi Network Compartment* , 2000, The Journal of Biological Chemistry.

[21]  P. Stanley Glycosylation mutants of animal cells. , 1984, Annual review of genetics.

[22]  T. Irimura,et al.  Distinct orders of GalNAc incorporation into a peptide with consecutive threonines. , 2001, Biochemical and biophysical research communications.

[23]  M. Hollingsworth,et al.  Cloning of a Human UDP-N-Acetyl-α-d-Galactosamine:PolypeptideN-Acetylgalactosaminyltransferase That Complements Other GalNAc-Transferases in Complete O-Glycosylation of the MUC1 Tandem Repeat* , 1998, The Journal of Biological Chemistry.

[24]  L. Tabak,et al.  Cloning and Expression of a Novel, Tissue Specifically Expressed Member of the UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase Family* , 1998, The Journal of Biological Chemistry.

[25]  G. Hart,et al.  Carbohydrates in chemistry and biology , 2000 .

[26]  J. Gordon,et al.  Glycans as legislators of host-microbial interactions: spanning the spectrum from symbiosis to pathogenicity. , 2001, Glycobiology.

[27]  H. Vennema,et al.  Structural Requirements for O-Glycosylation of the Mouse Hepatitis Virus Membrane Protein* , 1998, The Journal of Biological Chemistry.

[28]  S. Hintermann,et al.  Toward optimized carbohydrate-based anticancer vaccines: Epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewisy conjugates in mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  T. Imamura,et al.  The AATPAP sequence is a very efficient signal for O-glycosylation in CHO cells , 1999, Glycoconjugate Journal.

[30]  K. Tachibana,et al.  Molecular cloning and characterization of a novel member of the UDP‐GalNAc:polypeptide N‐acetylgalactosaminyltransferase family, pp‐GalNAc‐T12 1 , 2002 .

[31]  T. Imamura,et al.  Engineering neoglycoproteins with multiple O-glycans using repetitive pentapeptide glycosylation units , 2001, Glycoconjugate Journal.

[32]  S. Danishefsky,et al.  Conformational influences of glycosylation of a peptide: a possible model for the effect of glycosylation on the rate of protein folding. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  E. Nabel,et al.  Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury , 2000, Nature Medicine.

[34]  J. Marth,et al.  A genetic approach to Mammalian glycan function. , 2003, Annual review of biochemistry.

[35]  G. Davies Sweet secrets of synthesis , 2001, Nature Structural Biology.

[36]  S. Withers,et al.  Intermediate Trapping on a Mutant Retaining α-Galactosyltransferase Identifies an Unexpected Aspartate Residue* , 2004, Journal of Biological Chemistry.

[37]  S. Watson,et al.  An endothelial ligand for L-Selectin is a novel mucin-like molecule , 1992, Cell.

[38]  L. Tabak,et al.  Small molecule inhibitors of mucin-type O-linked glycosylation from a uridine-based library. , 2004, Chemistry & biology.

[39]  T. Meitinger,et al.  Molecular cloning of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, GalNAc-T8, and analysis as a candidate autosomal dominant hypophosphatemic rickets (ADHR) gene. , 2000, Gene.

[40]  T. A. Fritz,et al.  Disaccharide uptake and priming in animal cells: inhibition of sialyl Lewis X by acetylated Gal beta 1-->4GlcNAc beta-O-naphthalenemethanol. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[41]  K L Williams,et al.  Towards characterizing O-glycans: the relative merits of in vivo and in vitro approaches in seeking peptide motifs specifying O-glycosylation sites. , 1994, Glycobiology.

[42]  J. Lowe,et al.  Role of glycosylation in development. , 2003, Annual review of biochemistry.

[43]  S. Withers,et al.  Trapping of α-glycosidase intermediates , 2002 .

[44]  Derek Macmillan,et al.  Modular assembly of glycoproteins: towards the synthesis of GlyCAM-1 by using expressed protein ligation. , 2004, Angewandte Chemie.

[45]  F. Hanisch,et al.  O‐Linked glycans control glycoprotein processing by antigen‐presenting cells: a biochemical approach to the molecular aspects of MUC1 processing by dendritic cells , 2003, European journal of immunology.

[46]  P. Gleeson,et al.  Trafficking and localisation of resident Golgi glycosylation enzymes. , 2001, Biochimie.

[47]  J. Esko Genetic analysis of proteoglycan structure, function and metabolism. , 1991, Current opinion in cell biology.

[48]  C. Bertozzi,et al.  Homogeneous glycopeptides and glycoproteins for biological investigation. , 2002, Annual review of biochemistry.

[49]  S. Kuduk,et al.  Probing cell-surface architecture through synthesis: an NMR-determined structural motif for tumor-associated mucins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[50]  A. Helenius,et al.  Roles of N-linked glycans in the endoplasmic reticulum. , 2004, Annual review of biochemistry.

[51]  Å. Elhammer,et al.  The Lectin Domain of UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase 1 Is Involved in O-Glycosylation of a Polypeptide with Multiple Acceptor Sites* , 2002, The Journal of Biological Chemistry.

[52]  D. Kapitonov,et al.  Conserved domains of glycosyltransferases. , 1999, Glycobiology.

[53]  C. Bertozzi,et al.  Cell surface engineering by a modified Staudinger reaction. , 2000, Science.

[54]  G. Apodaca,et al.  Clathrin-mediated endocytosis of MUC1 is modulated by its glycosylation state. , 2000, Molecular biology of the cell.

[55]  G. Briand,et al.  Influence of the amino acid sequence on the MUC5AC motif peptide O-Glycosylation by Human gastric UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase(s) , 1998, Glycoconjugate Journal.

[56]  Zhenyu Zhang,et al.  Functional Characterization and Expression Analysis of Members of the UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase Family from Drosophila melanogaster* , 2003, Journal of Biological Chemistry.

[57]  L. Lichtenberger The hydrophobic barrier properties of gastrointestinal mucus. , 1995, Annual review of physiology.

[58]  Peter G. Schultz,et al.  A chemical switch for inhibitor-sensitive alleles of any protein kinase , 2000, Nature.

[59]  M. Gross,et al.  Influence of acceptor substrate primary amino acid sequence on the activity of human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase. Studies with the MUC1 tandem repeat. , 1994, The Journal of biological chemistry.

[60]  J. Esko,et al.  Expression Patterns of α2,3-Sialyltransferases and α1,3-Fucosyltransferases Determine the Mode of Sialyl Lewis X Inhibition by Disaccharide Decoys* , 2003, Journal of Biological Chemistry.

[61]  M. Mann,et al.  Proteomic analysis of post-translational modifications , 2003, Nature Biotechnology.

[62]  Bernd H. Müller,et al.  New Potent Sialyltransferase Inhibitors—Synthesis of Donor and of Transition‐State Analogues of Sialyl Donor CMP‐Neu5Ac , 1998 .

[63]  A. Gottschalk The Chemistry and Biology of Sialic Acids and Related Substances , 1960 .

[64]  A. Piro,et al.  Karl Landsteiner: a hundred years later. , 2001, Transplantation.

[65]  P. Roepstorff,et al.  UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Identification and separation of two distinct transferase activities. , 1995, The Journal of biological chemistry.

[66]  Kan Yang,et al.  Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2 , 2002, Science.

[67]  D. Skropeta,et al.  Stereoselective synthesis of phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors. , 2003, Bioorganic & medicinal chemistry letters.

[68]  P. Schultz,et al.  Expanding the genetic code. , 2002, Chemical communications.

[69]  L. Tabak,et al.  Structure-function analysis of the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Essential residues lie in a predicted active site cleft resembling a lactose repressor fold. , 1999, The Journal of biological chemistry.

[70]  L. Tabak,et al.  Charge Distribution of Flanking Amino Acids Influences O-Glycan Acquisition in Vivo(*) , 1996, The Journal of Biological Chemistry.

[71]  M. Pasumarthy,et al.  Determination of the Site-specific O-Glycosylation Pattern of the Porcine Submaxillary Mucin Tandem Repeat Glycopeptide , 1997, The Journal of Biological Chemistry.

[72]  R. Hill,et al.  The acceptor substrate specificity of porcine submaxillary UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is dependent on the amino acid sequences adjacent to serine and threonine residues. , 1993, The Journal of biological chemistry.

[73]  S. Withers,et al.  Mutagenesis of glycosidases. , 1999, Annual review of biochemistry.

[74]  K. Ley,et al.  Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation , 2004, Nature Reviews Immunology.

[75]  M. Hollingsworth,et al.  A novel human UDP‐N‐acetyl‐D‐galactosamine:polypeptide N‐acetylgalactosaminyltransferase, GalNAc‐T7, with specificity for partial GalNAc‐glycosylated acceptor substrates , 1999, FEBS letters.

[76]  D. Kingsley,et al.  Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal UDP-GalNAc 4-epimerase deficient mutant , 1986, Cell.

[77]  R. Hill,et al.  Purification and characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase specific for glycosylation of threonine residues. , 1992, The Journal of biological chemistry.

[78]  J. Marth Complexity in O-linked oligosaccharide biosynthesis engendered by multiple polypeptide N-acetylgalactosaminyltransferases. , 1996, Glycobiology.

[79]  V. Piller,et al.  Synthesis and biological evaluation of new UDP-GalNAc analogues for the study of polypeptide-α-GalNAc-transferases , 2003 .

[80]  M. Fukuda Roles of mucin-type O-glycans in cell adhesion. , 2002, Biochimica et biophysica acta.

[81]  Chong Yu,et al.  A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[82]  O Hindsgaul,et al.  Bovine α1,3‐galactosyltransferase catalytic domain structure and its relationship with ABO histo‐blood group and glycosphingolipid glycosyltransferases , 2001, The EMBO journal.

[83]  L. Tabak,et al.  Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo. , 1998, Glycobiology.

[84]  H. Ikenaga,et al.  Discovery of the Shortest Sequence Motif for High Level Mucin-type O-Glycosylation* , 1997, The Journal of Biological Chemistry.

[85]  L. Tabak,et al.  Cloning and Characterization of a Ninth Member of the UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase Family, ppGaNTase-T9* , 2001, The Journal of Biological Chemistry.

[86]  Å. Elhammer,et al.  Function of the lectin domain of polypeptide N-acetylgalactosaminyltransferase 1. , 2002, Biochemical and biophysical research communications.

[87]  A. F. Bradbury,et al.  Substrate recognition by UDP-N-acetyl-α-d-galactosamine: polypeptide N-acetyl-α-d-galactosaminyltransferase. Effects of chain length and disulphide bonding of synthetic peptide substrates , 1988 .

[88]  E. Nabel,et al.  Ebola Virus Glycoprotein Toxicity Is Mediated by a Dynamin-Dependent Protein-Trafficking Pathway , 2005, Journal of Virology.

[89]  G. Forstner Signal transduction, packaging and secretion of mucins. , 1995, Annual review of physiology.

[90]  D. Dowbenko,et al.  Structure and chromosomal localization of the murine gene encoding GLYCAM 1. A mucin-like endothelial ligand for L selectin. , 1993, The Journal of biological chemistry.

[91]  H. Narimatsu,et al.  Initiation of O-Glycan Synthesis in IgA1 Hinge Region Is Determined by a Single Enzyme, UDP-N-Acetyl-α-d-galactosamine:PolypeptideN-Acetylgalactosaminyltransferase 2* , 2003, The Journal of Biological Chemistry.

[92]  L. Tabak,et al.  Diverse spatial expression patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase family member mRNAs during mouse development. , 2000, Glycobiology.

[93]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.

[94]  H. Nakada,et al.  High density O-glycosylation of the MUC2 tandem repeat unit by N-acetylgalactosaminyltransferase-3 in colonic adenocarcinoma extracts. , 2001, Cancer research.

[95]  Peter G. Schultz,et al.  A New Strategy for the Synthesis of Glycoproteins , 2004, Science.

[96]  S. Tsuboi,et al.  Roles of O‐linked oligosaccharides in immune responses , 2000, Bioessays.

[97]  L. Lasky,et al.  Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin , 1993, Nature.

[98]  C. Bertozzi,et al.  Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. , 1997, Science.

[99]  D. Roos,et al.  cDNA cloning and expression of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase T1 from Toxoplasma gondii. , 2003, Molecular and biochemical parasitology.

[100]  D. Weghuis,et al.  Genomic organization and chromosomal localization of three members of the UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyltransferase family. , 1998, Glycobiology.

[101]  A. Imberty,et al.  Fold recognition and molecular modeling of a lectin-like domain in UDP-GalNac:polypeptide N-acetylgalactosaminyltransferases. , 1997, Protein engineering.

[102]  T. Muir Semisynthesis of proteins by expressed protein ligation. , 2003, Annual review of biochemistry.

[103]  H. Hauri,et al.  Localization of O-glycan initiation, sphingomyelin synthesis, and glucosylceramide synthesis in Vero cells with respect to the endoplasmic reticulum-Golgi intermediate compartment. , 1994, The Journal of biological chemistry.

[104]  D. Behar,et al.  Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders , 2005, Journal of Molecular Medicine.

[105]  J. Peter-Katalinic,et al.  Dynamic epigenetic regulation of initial O-glycosylation by UDP-N-Acetylgalactosamine:Peptide N-acetylgalactosaminyltransferases. site-specific glycosylation of MUC1 repeat peptide influences the substrate qualities at adjacent or distant Ser/Thr positions. , 1999, The Journal of biological chemistry.

[106]  V. Gouyer,et al.  1-Benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside Blocks the Apical Biosynthetic Pathway in Polarized HT-29 Cells* , 2003, Journal of Biological Chemistry.

[107]  J. Esko,et al.  Fucosylation of Disaccharide Precursors of Sialyl LewisX Inhibit Selectin-mediated Cell Adhesion* , 1997, The Journal of Biological Chemistry.

[108]  K. Tachibana,et al.  Cloning and characterization of a novel UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, pp-GalNAc-T14. , 2003, Biochemical and biophysical research communications.

[109]  Ruth Lloyd,et al.  Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA. , 2002, Chemistry & biology.

[110]  Joseph Shiloach,et al.  The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[111]  C. Bertozzi,et al.  Metabolic oligosaccharide engineering as a tool for glycobiology. , 2003, Current opinion in chemical biology.

[112]  I. Brockhausen Pathways of O-glycan biosynthesis in cancer cells. , 1999, Biochimica et biophysica acta.

[113]  P. Primakoff,et al.  Penetration, Adhesion, and Fusion in Mammalian Sperm-Egg Interaction , 2002, Science.

[114]  M. Gross,et al.  N-acetylgalactosamine glycosylation of MUC1 tandem repeat peptides by pancreatic tumor cell extracts. , 1994, Cancer research.

[115]  L. Tabak,et al.  An Inhibitor of O-Glycosylation Induces Apoptosis in NIH3T3 Cells and Developing Mouse Embryonic Mandibular Tissues* , 2004, Journal of Biological Chemistry.

[116]  C. Bertozzi,et al.  Golgi Localization of Carbohydrate Sulfotransferases Is a Determinant of L-selectin Ligand Biosynthesis* , 2003, Journal of Biological Chemistry.

[117]  T. Irimura,et al.  Order and maximum incorporation of N-acetyl-D-galactosamine into threonine residues of MUC2 core peptide with microsome fraction of human-colon-carcinoma LS174T cells. , 2000, The Biochemical journal.

[118]  R. Hill,et al.  Subcellular localization of the UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-mediated O-glycosylation reaction in the submaxillary gland. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[119]  M. Hollingsworth,et al.  Cloning and Characterization of a Close Homologue of Human UDP-N-acetyl-α-d-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase-T3, Designated GalNAc-T6 , 1999, The Journal of Biological Chemistry.

[120]  T. Darden,et al.  Glucosaminylglycan biosynthesis: what we can learn from the X-ray crystal structures of glycosyltransferases GlcAT1 and EXTL2. , 2003, Biochemical and biophysical research communications.

[121]  Chi‐Huey Wong,et al.  A Potent and Highly Selective Inhibitor of Human α-1,3-Fucosyltransferase via Click Chemistry , 2003 .

[122]  Carolyn R. Bertozzi,et al.  Chemical Glycobiology , 2001, Science.

[123]  R. Hill,et al.  The Structure and Assembly of Secreted Mucins* 210 , 1999, The Journal of Biological Chemistry.

[124]  J. Young,et al.  Enzymic O-glycosylation of synthetic peptides from sequences in basic myelin protein. , 1979, Biochemistry.

[125]  S. P. Andrews,et al.  Investigation of the requirements for O-glycosylation by bovine submaxillary gland UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosamine transferase using synthetic peptide substrates. , 1981, The Journal of biological chemistry.

[126]  L. Tabak,et al.  Kinetic Analysis of a Recombinant UDP-N-acetyl-D-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase (*) , 1995, The Journal of Biological Chemistry.

[127]  F. Homa,et al.  Organization of a human UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase gene and a related processed pseudogene. , 1996, Glycobiology.

[128]  L. Tabak,et al.  Light and electron microscopic immunolocalization of rat submandibular gland mucin glycoprotein and glutamine/glutamic acid-rich proteins. , 1989, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[129]  L. Tabak,et al.  Purification, cloning, and expression of a bovine UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferase. , 1993, The Journal of biological chemistry.

[130]  L. Tabak,et al.  Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling. , 2004, Chemistry & biology.

[131]  Carolyn R. Bertozzi,et al.  Essentials of Glycobiology , 1999 .

[132]  K. Chou,et al.  Support vector machines for predicting the specificity of GalNAc-transferase , 2002, Peptides.

[133]  E. Berger,et al.  Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus. , 1998, Journal of cell science.

[134]  L. Tabak,et al.  Charge distribution of flanking amino acids inhibits O-glycosylation of several single-site acceptors in vivo. , 1997, Glycobiology.

[135]  S. Gendler,et al.  Epithelial mucin genes. , 1995, Annual review of physiology.

[136]  J. Gordon,et al.  Commensal Host-Bacterial Relationships in the Gut , 2001, Science.

[137]  F. Real,et al.  GalNAc-α-O-benzyl Inhibits NeuAcα2-3 Glycosylation and Blocks the Intracellular Transport of Apical Glycoproteins and Mucus in Differentiated HT-29 Cells , 1998, The Journal of cell biology.

[138]  G. Hannon RNA interference : RNA , 2002 .

[139]  S. Kornfeld,et al.  Assembly of asparagine-linked oligosaccharides. , 1985, Annual review of biochemistry.

[140]  T. Gerken,et al.  Mucin Core O-Glycosylation Is Modulated by Neighboring Residue Glycosylation Status , 2002, The Journal of Biological Chemistry.

[141]  G J Strous,et al.  Mucin-type glycoproteins. , 1992, Critical reviews in biochemistry and molecular biology.

[142]  L. Tabak,et al.  cDNA Cloning and Expression of a Novel UDP-N-acetyl-d-galactosamine:PolypeptideN-Acetylgalactosaminyltransferase* , 1997, The Journal of Biological Chemistry.

[143]  E. Bennett,et al.  Purification and cDNA Cloning of a Human UDP-N-acetyl-α- D-galactosamine:polypeptide N-Acetylgalactosaminyltransferase (*) , 1995, The Journal of Biological Chemistry.

[144]  R. Dwek,et al.  Glycosylation and the immune system. , 2001, Science.

[145]  M. Jakobsen,et al.  Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family. , 1999, Glycobiology.

[146]  P. Rudd,et al.  Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. , 2001, The Journal of biological chemistry.

[147]  M. Hollingsworth,et al.  The contribution of tandem repeat number to the O-glycosylation of mucins. , 2003, Glycobiology.

[148]  F. Real,et al.  Benzyl-N-acetyl-α-d-galactosaminide Induces a Storage Disease-like Phenotype by Perturbing the Endocytic Pathway* , 2003, The Journal of Biological Chemistry.

[149]  R. Poorman,et al.  The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase as inferred from a database of in vivo substrates and from the in vitro glycosylation of proteins and peptides. , 1993, The Journal of biological chemistry.

[150]  S. Kuduk,et al.  Principles of mucin architecture: structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains. , 2002, Journal of the American Chemical Society.

[151]  S. Müller,et al.  MUC1: the polymorphic appearance of a human mucin. , 2000, Glycobiology.

[152]  R. Geyer,et al.  Structures of the major carbohydrates of natural human interleukin-2. , 1985, European journal of biochemistry.

[153]  Peter Roepstorff,et al.  Functional Conservation of Subfamilies of Putative UDP-N-acetylgalactosamine:Polypeptide N-Acetylgalactosaminyltransferases inDrosophila, Caenorhabditis elegans, and Mammals , 2002, The Journal of Biological Chemistry.

[154]  T. Irimura,et al.  O-GalNAc incorporation into a cluster acceptor site of three consecutive threonines. Distinct specificity of GalNAc-transferase isoforms. , 2002, European journal of biochemistry.

[155]  S. Danishefsky,et al.  On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[156]  S. Brunak,et al.  Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites. , 2005, Glycobiology.

[157]  Keith Brew,et al.  Roles of individual enzyme-substrate interactions by alpha-1,3-galactosyltransferase in catalysis and specificity. , 2003, Biochemistry.

[158]  Å. Elhammer,et al.  Identification of two cysteine residues involved in the binding of UDP-GalNAc to UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1 (GalNAc-T1). , 2002, European journal of biochemistry.

[159]  Anthony C. Bishop,et al.  Unnatural ligands for engineered proteins: new tools for chemical genetics. , 2000, Annual review of biophysics and biomolecular structure.

[160]  Y. Kim,et al.  Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells. , 1989, The Journal of biological chemistry.

[161]  T. Irimura,et al.  Incorporation of N‐acetylgalactosamine into consecutive threonine residues in MUC2 tandem repeat by recombinant human N‐acetyl‐D‐galactosamine transferase‐T1, T2 and T3 , 1999, FEBS letters.

[162]  M. Hollingsworth,et al.  The Lectin Domain of UDP-N-acetyl-d-galactosamine:PolypeptideN-acetylgalactosaminyltransferase-T4 Directs Its Glycopeptide Specificities* , 2000, The Journal of Biological Chemistry.

[163]  B. Imperiali Protein Glycosylation: The Clash of the Titans , 1997 .

[164]  L. Tabak,et al.  Identification of essential histidine residues in UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T1. , 1997, The Biochemical journal.

[165]  Andrew Gooley,et al.  Localization of O-Glycosylation Sites on Glycopeptide Fragments from Lactation-associated MUC1 , 1997, The Journal of Biological Chemistry.

[166]  Bernard Henrissat,et al.  An evolving hierarchical family classification for glycosyltransferases. , 2003, Journal of molecular biology.

[167]  T. Irimura,et al.  N-acetylgalactosamine incorporation into a peptide containing consecutive threonine residues by UDP-N-acetyl-D-galactosaminide:polypeptide N-acetylgalactosaminyltransferases. , 2001, Glycobiology.

[168]  G. Briand,et al.  Analysis by electrospray mass spectrometry of glycopeptides from the in vitro O-glycosylation reaction using human mucin motif peptide. , 1994, Analytical biochemistry.

[169]  L. Tabak,et al.  The influence of flanking sequence on the O-glycosylation of threonine in vitro. , 1992, The Journal of biological chemistry.

[170]  Carolyn R Bertozzi,et al.  A chemical approach for identifying O-GlcNAc-modified proteins in cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[171]  M. Sinnott,et al.  Catalytic mechanism of enzymic glycosyl transfer , 1990 .

[172]  W. Watkins Blood-group substances. , 1966, Science.

[173]  D. Behar,et al.  Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis , 2004, Nature Genetics.

[174]  Chi‐Huey Wong,et al.  Emerging themes in medicinal glycoscience , 2000, Nature Biotechnology.

[175]  Monica M. Palcic,et al.  The structural basis for specificity in human ABO(H) blood group biosynthesis , 2002, Nature Structural Biology.

[176]  D. Hinrichsen,et al.  Mammalian alpha-acetylgalactosaminidase. Occurrence, partial purification, and action on linkages in submaxillary mucins. , 1969, Biochemistry.

[177]  R. Cummings,et al.  Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[178]  Raymond A. Dwek,et al.  Targeting glycosylation as a therapeutic approach , 2002, Nature Reviews Drug Discovery.

[179]  L. Tabak,et al.  T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[180]  F. Homa,et al.  Isolation and expression of a cDNA clone encoding a bovine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. , 1993, The Journal of biological chemistry.

[181]  F. Hanisch,et al.  Evidence for glycosylation-dependent activities of polypeptide N-acetylgalactosaminyltransferases rGalNAc-T2 and -T4 on mucin glycopeptides. , 2001, Glycobiology.

[182]  M. Pasumarthy,et al.  Site-specific Core 1 O-Glycosylation Pattern of the Porcine Submaxillary Gland Mucin Tandem Repeat , 1998, The Journal of Biological Chemistry.

[183]  G. J. Swaminathan,et al.  Structure of UDP Complex of UDP-galactose:β-Galactoside-α-1,3-galactosyltransferase at 1.53-Å Resolution Reveals a Conformational Change in the Catalytically Important C Terminus* , 2001, The Journal of Biological Chemistry.

[184]  Chi‐Huey Wong,et al.  Synthesis of N‐Acetyllactosamine Derivatives with Variation in the Aglycon Moiety for the Study of Inhibition of Sialyl Lewis x Expression , 2003, Chembiochem : a European journal of chemical biology.

[185]  H. Itoh,et al.  Expression of UDP‐N‐acetyl‐α‐D‐galactosamine–polypeptide galNAc N‐acetylgalactosaminyl transferase‐3 in relation to differentiation and prognosis in patients with colorectal carcinoma , 2002, Cancer.

[186]  L. Tabak In defense of the oral cavity: structure, biosynthesis, and function of salivary mucins. , 1995, Annual review of physiology.

[187]  J. Taylor‐Papadimitriou,et al.  MUC1 and cancer. , 1999, Biochimica et biophysica acta.

[188]  S. Rosen Ligands for L-selectin: homing, inflammation, and beyond. , 2004, Annual review of immunology.

[189]  C. Bertozzi,et al.  An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based library: a strategy to inhibit O-linked glycosylation. , 2002, Chemistry & biology.

[190]  Xiao-tao Chen,et al.  Convergent total synthesis of a tumour-associated mucin motif , 1997, Nature.

[191]  L. Tabak,et al.  Cloning and expression of mouse UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3. , 1996, Biochemical and biophysical research communications.

[192]  G. J. Swaminathan,et al.  Structural Basis of Ordered Binding of Donor and Acceptor Substrates to the Retaining Glycosyltransferase, α-1,3-Galactosyltransferase* , 2002, The Journal of Biological Chemistry.

[193]  T. Gerken,et al.  Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin. , 1989, Biochemistry.

[194]  C. Bertozzi,et al.  Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface engineering. , 2001, Journal of the American Chemical Society.

[195]  M. Hollingsworth,et al.  Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines. , 1997, Cancer research.

[196]  A. Elbein,et al.  Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. , 1987, Annual review of biochemistry.

[197]  S. Batra,et al.  In vivo glycosylation of mucin tandem repeats. , 2001, Glycobiology.

[198]  Chemoenzymatic Synthesis of Biotinylated Nucleotide Sugars as Substrates for Glycosyltransferases , 2001, Chembiochem : a European journal of chemical biology.

[199]  R. Schmidt,et al.  Efficient sialyltransferase inhibitors based on glycosides of N-acetylglucosamine. , 2002, Journal of the American Chemical Society.

[200]  Lawrence A Tabak,et al.  All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. , 2003, Glycobiology.

[201]  Allen,et al.  From the Laboratory to the Clinic: A Retrospective on Fully Synthetic Carbohydrate-Based Anticancer Vaccines Frequently used abbreviations are listed in the appendix. , 2000, Angewandte Chemie.

[202]  M. Konishi,et al.  Brain-specific expression of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T9). , 2000, Biochimica et biophysica acta.

[203]  F. Hanisch,et al.  O-Glycosylation of the Mucin Type , 2001, Biological chemistry.

[204]  M. Hollingsworth,et al.  Expression of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer , 2000, Journal of Gastroenterology.

[205]  K. Nehrke,et al.  cDNA Cloning and Expression of a Family of UDP-N-acetyl-dgalactosamine:PolypeptideN-Acetylgalactosaminyltransferase Sequence Homologs fromCaenorhabditis elegans * , 1998, The Journal of Biological Chemistry.

[206]  C. Bertozzi,et al.  Probing glycosyltransferase activities with the Staudinger ligation. , 2004, Journal of the American Chemical Society.

[207]  K. Butenhof,et al.  Effects of glycosylation on the conformation and dynamics of O-linked glycoproteins: carbon-13 NMR studies of ovine submaxillary mucin. , 1989, Biochemistry.

[208]  J. Marth,et al.  Cloning and Characterization of a New Human UDP-N-Acetyl-α-d-galactosamine:PolypeptideN-Acetylgalactosaminyltransferase, Designated pp-GalNAc-T13, That Is Specifically Expressed in Neurons and Synthesizes GalNAc α-Serine/Threonine Antigen* , 2003, The Journal of Biological Chemistry.

[209]  C. Bertozzi,et al.  Metabolic labeling of glycoproteins with chemical tags through unnatural sialic acid biosynthesis. , 2000, Methods in enzymology.

[210]  R. Cummings,et al.  Glycosulfopeptides with O-Glycans Containing Sialylated and Polyfucosylated Polylactosamine Bind with Low Affinity to P-selectin* , 2002, The Journal of Biological Chemistry.

[211]  C. Bertozzi,et al.  Constructing azide-labeled cell surfaces using polysaccharide biosynthetic pathways. , 2003, Methods in enzymology.

[212]  K. Tachibana,et al.  Characterization of a novel human UDP‐GalNAc transferase, pp‐GalNAc‐T101 , 2002 .

[213]  R. Schmidt,et al.  Nitroglycal Concatenation: A Broadly Applicable and Efficient Approach to the Synthesis of Complex O-Glycans. , 2001, Angewandte Chemie.

[214]  S. Roseman,et al.  Enzymatic synthesis of the protein-hexosamine linkage in sheep submaxillary mucin. , 1967, The Journal of biological chemistry.

[215]  F. Burnet Haemagglutination in relation to host cell-virus interaction. , 1952, Annual review of microbiology.

[216]  Anne-Lise Veuthey,et al.  Annotation of glycoproteins in the SWISS‐PROT database , 2001 .

[217]  L. Otvos,et al.  Complex Carbohydrates Are Not Removed During Processing of Glycoproteins by Dendritic Cells , 2002, The Journal of experimental medicine.

[218]  S. Müller,et al.  Recombinant MUC1 Probe Authentically Reflects Cell-specific O-Glycosylation Profiles of Endogenous Breast Cancer Mucin , 2002, The Journal of Biological Chemistry.

[219]  B Henrissat,et al.  Glycoside hydrolases and glycosyltransferases: families and functional modules. , 2001, Current opinion in structural biology.

[220]  Lawrence A Tabak,et al.  Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase isoforms in murine tissues determined by real-time PCR: a new view of a large family. , 2003, Glycobiology.

[221]  L. Tabak,et al.  A Comparison of Serine and Threonine O-Glycosylation by UDP-GaINAc:Polypeptide N-Acetylgalactosaminyltransferase , 1993, Journal of dental research.

[222]  E. Bennett,et al.  cDNA cloning and expression of a novel human UDP-N-acetyl-alpha-D-galactosamine. Polypeptide N-acetylgalactosaminyltransferase, GalNAc-t3. , 1996, The Journal of biological chemistry.

[223]  S. Kornfeld,et al.  Purification and characterization of UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyltransferase from bovine colostrum and murine lymphoma BW5147 cells. , 1986, The Journal of biological chemistry.

[224]  A. Varki,et al.  Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[225]  S. Withers,et al.  Mechanistic Studies of a Retaining α-Galactosyltransferase from Neisseria meningitidis† , 2002 .

[226]  M. Hermiston,et al.  CD45: a critical regulator of signaling thresholds in immune cells. , 2003, Annual review of immunology.

[227]  V. Garcia-Campayo,et al.  Evolution of Lutropin to Chorionic Gonadotropin Generates a Specific Routing Signal for Apical Release in Vivo * , 2002, The Journal of Biological Chemistry.

[228]  F. Hanisch,et al.  Studies on the order and site specificity of GalNAc transfer to MUC1 tandem repeats by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase from milk or mammary carcinoma cells. , 1995, European journal of biochemistry.