Thomas A Gerken

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. pmc Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs
    Thomas A Gerken
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    Glycobiology 18:861-70. 2008
  2. doi request reprint O-glycoprotein biosynthesis: site localization by Edman degradation and site prediction based on random peptide substrates
    Thomas A Gerken
    Department of Pediatrics and Biochemistry, Case Western Reserve University, School of Medicine, Cleveland, OH, USA
    Methods Mol Biol 842:81-108. 2012
  3. pmc Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases
    Thomas A Gerken
    Department of Pediatrics W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 286:14493-507. 2011
  4. ncbi request reprint Kinetic modeling confirms the biosynthesis of mucin core 1 (beta-Gal(1-3) alpha-GalNAc-O-Ser/Thr) O-glycan structures are modulated by neighboring glycosylation effects
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Biochemistry 43:4137-42. 2004
  5. ncbi request reprint Role of peptide sequence and neighboring residue glycosylation on the substrate specificity of the uridine 5'-diphosphate-alpha-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferases T1 and T2: kinetic modeling of the porcine and canine sub
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4948, USA
    Biochemistry 43:9888-900. 2004
  6. ncbi request reprint Mucin core O-glycosylation is modulated by neighboring residue glycosylation status. Kinetic modeling of the site-specific glycosylation of the apo-porcine submaxillary mucin tandem repeat by UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases T1 an
    Thomas A Gerken
    Departments of Pediatrics and Biochemistry, W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA
    J Biol Chem 277:49850-62. 2002
  7. pmc Glycopeptide-preferring polypeptide GalNAc transferase 10 (ppGalNAc T10), involved in mucin-type O-glycosylation, has a unique GalNAc-O-Ser/Thr-binding site in its catalytic domain not found in ppGalNAc T1 or T2
    Cynthia L Perrine
    Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 4948, USA
    J Biol Chem 284:20387-97. 2009
  8. ncbi request reprint Determination of the site-specific oligosaccharide distribution of the O-glycans attached to the porcine submaxillary mucin tandem repeat. Further evidence for the modulation of O-glycans side chain structures by peptide sequence
    Thomas A Gerken
    Department of Pediatrics, W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 277:7736-51. 2002
  9. ncbi request reprint Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 and T2 derived from oriented random peptide substrates
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Departments of Pediatrics and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Biol Chem 281:32403-16. 2006
  10. pmc Conserved sequence in the aggrecan interglobular domain modulates cleavage by ADAMTS-4 and ADAMTS-5
    Hazuki E Miwa
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1790:161-72. 2009

Research Grants

  1. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas Gerken; Fiscal Year: 2009
  2. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas Gerken; Fiscal Year: 2007
  3. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas A Gerken; Fiscal Year: 2010

Collaborators

  • Lawrence A Tabak
  • Thomas M Hering
  • Kelley Moremen
  • Wei Shen
  • Jian He
  • Tongzhong Ju
  • Pamela B Davis
  • Richard Cummings
  • J B Lowe
  • C R Bertozzi
  • B S Cavada
  • Matthew R Pratt
  • Howard C Hang
  • Hazuki E Miwa
  • Jayalakshmi Raman
  • Cynthia L Perrine
  • Kishore Guda
  • Cynthia Perrine
  • Oliver Jamison
  • Timothy A Fritz
  • Tru D Huynh
  • Tarun K Dam
  • Santosh K Ghosh
  • Kelly G Ten Hagen
  • Junxia Xie
  • Earl Lawrence
  • James K V Willson
  • James Lutterbaugh
  • Helen Moinova
  • Bert Vogelstein
  • Leanna Natale
  • Sanford D Markowitz
  • Nikolas Papadopoulos
  • Lakshmeswari Ravi
  • Jill Barnholtz-Sloan
  • Anjali Ganguli
  • Meghan Cotter
  • Susan Lewis
  • Peng Wu
  • Joseph Willis
  • Georgia L Wiesner
  • Dawn W Dawson
  • Victor E Velculescu
  • Lori R Duesler
  • Kenneth W Kinzler
  • Giovanni Parmigiani
  • Mian Liu
  • David Live
  • Aaron Weinberg
  • Zhimin Feng
  • Keith M Schneider
  • Kyria S Nascimento
  • Tales R Moura
  • C Fred Brewer
  • Thomas S McCormick
  • David M Flory
  • Zhenyu Zhang
  • David S Stein
  • Duy T Tran
  • Jiying Zhao
  • Jianjie Ma
  • Lynn M Adams

Detail Information

Publications21

  1. pmc Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs
    Thomas A Gerken
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    Glycobiology 18:861-70. 2008
    ....
  2. doi request reprint O-glycoprotein biosynthesis: site localization by Edman degradation and site prediction based on random peptide substrates
    Thomas A Gerken
    Department of Pediatrics and Biochemistry, Case Western Reserve University, School of Medicine, Cleveland, OH, USA
    Methods Mol Biol 842:81-108. 2012
    ....
  3. pmc Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases
    Thomas A Gerken
    Department of Pediatrics W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 286:14493-507. 2011
    ..We conclude that each ppGalNAc T isoform may be uniquely sensitive to peptide sequence and overall charge, which together dictates the substrate sites that will be glycosylated...
  4. ncbi request reprint Kinetic modeling confirms the biosynthesis of mucin core 1 (beta-Gal(1-3) alpha-GalNAc-O-Ser/Thr) O-glycan structures are modulated by neighboring glycosylation effects
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Biochemistry 43:4137-42. 2004
    ..As a result, the development of approaches for predicting O-glycan core structures in a site-specific manner may now appear a distinct possibility...
  5. ncbi request reprint Role of peptide sequence and neighboring residue glycosylation on the substrate specificity of the uridine 5'-diphosphate-alpha-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferases T1 and T2: kinetic modeling of the porcine and canine sub
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4948, USA
    Biochemistry 43:9888-900. 2004
    ....
  6. ncbi request reprint Mucin core O-glycosylation is modulated by neighboring residue glycosylation status. Kinetic modeling of the site-specific glycosylation of the apo-porcine submaxillary mucin tandem repeat by UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases T1 an
    Thomas A Gerken
    Departments of Pediatrics and Biochemistry, W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA
    J Biol Chem 277:49850-62. 2002
    ....
  7. pmc Glycopeptide-preferring polypeptide GalNAc transferase 10 (ppGalNAc T10), involved in mucin-type O-glycosylation, has a unique GalNAc-O-Ser/Thr-binding site in its catalytic domain not found in ppGalNAc T1 or T2
    Cynthia L Perrine
    Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 4948, USA
    J Biol Chem 284:20387-97. 2009
    ..Our results reveal that these transferases have unique peptide and glycopeptide preferences demonstrating their substrate diversity and their likely roles ranging from initiating transferases to filling-in transferases...
  8. ncbi request reprint Determination of the site-specific oligosaccharide distribution of the O-glycans attached to the porcine submaxillary mucin tandem repeat. Further evidence for the modulation of O-glycans side chain structures by peptide sequence
    Thomas A Gerken
    Department of Pediatrics, W A Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 277:7736-51. 2002
    ....
  9. ncbi request reprint Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 and T2 derived from oriented random peptide substrates
    Thomas A Gerken
    W A Bernbaum Center for Cystic Fibrosis Research, Departments of Pediatrics and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Biol Chem 281:32403-16. 2006
    ..Such information will be invaluable for identifying isoform-specific peptide acceptors, creating isoform-specific substrates, and predicting O-glycosylation sites...
  10. pmc Conserved sequence in the aggrecan interglobular domain modulates cleavage by ADAMTS-4 and ADAMTS-5
    Hazuki E Miwa
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1790:161-72. 2009
    ..Cleavage of aggrecan by ADAMTS proteinases at specific sites within highly conserved regions may be important to normal physiological enzyme functions, as well as pathological degradation...
  11. ncbi request reprint Effects of covalently attached chondroitin sulfate on aggrecan cleavage by ADAMTS-4 and MMP-13
    Hazuki E Miwa
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Matrix Biol 25:534-45. 2006
    ..These data indicate that covalently bound CS enhances ADAMTS-4-mediated cleavage within the CS-rich region. MMP-13 also cleaves preferentially within the CS-region, but by an apparently CS-independent mechanism...
  12. pmc The lectin domain of the polypeptide GalNAc transferase family of glycosyltransferases (ppGalNAc Ts) acts as a switch directing glycopeptide substrate glycosylation in an N- or C-terminal direction, further controlling mucin type O-glycosylation
    Thomas A Gerken
    Department of Pediatrics, WA Bernbaum Center for Cystic Fibrosis Research, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 288:19900-14. 2013
    ....
  13. ncbi request reprint A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification
    Junxia Xie
    Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 277:23019-27. 2002
    ..We speculate that the NEG2 region interacts with other cytosolic domains of CFTR to control opening and closing transitions of the chloride channel...
  14. pmc Systematic determination of the peptide acceptor preferences for the human UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase)
    Cynthia Perrine
    Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    Glycobiology 19:321-8. 2009
    ..This work suggests that there are indeed subtle specific and nonspecific protein-targeting sequence motifs for this transferase...
  15. pmc Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers
    Kishore Guda
    Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 106:12921-5. 2009
    ..These findings suggest that genetic defects in the O-glycosylation pathway in part underlie aberrant glycosylation in colon cancers, and they contribute to the development of a subset of these malignancies...
  16. ncbi request reprint Mammalian expression of full-length bovine aggrecan and link protein: formation of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by ADAMTS-4 and MMP-13
    Hazuki E Miwa
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1760:472-86. 2006
    ....
  17. ncbi request reprint Quantification of human beta-defensin-2 and -3 in body fluids: application for studies of innate immunity
    Santosh K Ghosh
    Department of Biological Sciences, Case School of Dental Medicine, Cleveland, OH 44106 4905, USA
    Clin Chem 53:757-65. 2007
    ..Human beta-defensins (hBDs) are epithelial cell-derived antimicrobial and immunoregulatory cationic peptides. Our objective was to establish an analytical tool to quantify inducible hBD-2 and -3 in body fluids...
  18. ncbi request reprint Functional characterization and expression analysis of members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family from Drosophila melanogaster
    Kelly G Ten Hagen
    Section of Biological Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:35039-48. 2003
    ..The characterization reported here provides additional insight into the use of this model system to dissect the biological role of this enzyme family in vivo during both fly and mammalian development...
  19. ncbi request reprint Binding studies of alpha-GalNAc-specific lectins to the alpha-GalNAc (Tn-antigen) form of porcine submaxillary mucin and its smaller fragments
    Tarun K Dam
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 282:28256-63. 2007
    ..The results have important implications for the biological activities of mucins including those expressing the Tn cancer antigen...
  20. pmc The catalytic and lectin domains of UDP-GalNAc:polypeptide alpha-N-Acetylgalactosaminyltransferase function in concert to direct glycosylation site selection
    Jayalakshmi Raman
    Section on Biological Chemistry, NIDDK, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
    J Biol Chem 283:22942-51. 2008
    ..Local sequence recognition by the catalytic domain differs between hT2 and hT10 in that hT10 requires a pre-existing GalNAc residue while hT2 does not...
  21. ncbi request reprint Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling
    Matthew R Pratt
    Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA
    Chem Biol 11:1009-16. 2004
    ..The data suggest that the ppGalNAcTs can be classified into at least four types, which working together, are able to produce densely glycosylated mucin glycoproteins...

Research Grants11

  1. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas Gerken; Fiscal Year: 2009
    ..It is anticipated that these studies will lead to potential modalities for the detection, prevention, and/or treatment of colon cancer and other diseases. ..
  2. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas Gerken; Fiscal Year: 2007
    ..Fundamental tools for the rational prediction of site specific O-glycan structures will result from these studies. ..
  3. MUCIN SITE SPECIFIC O-GLYCOSYLATION
    Thomas A Gerken; Fiscal Year: 2010
    ..It is anticipated that these studies will lead to potential modalities for the detection, prevention, and/or treatment of colon cancer and other diseases. ..