In vivo glycosylation of mucin tandem repeats

Howard S. Silverman, Simon Parry, Mark Sutton-Smith, Michael D. Burdick, Kimberly McDermott, Colm J. Reid, Surinder K. Batra, Howard R. Morris, Michael A. Hollingsworth, Anne Dell, Ann Harris

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. Future applications of these chimeras will include investigations of mucin post-translational modification in the context of disease.

Original languageEnglish (US)
Pages (from-to)459-471
Number of pages13
JournalGlycobiology
Volume11
Issue number6
StatePublished - 2001
Externally publishedYes

Fingerprint

Glycosylation
Tandem Repeat Sequences
Mucins
Tumor-Associated Carbohydrate Antigens
Fast Atom Bombardment Mass Spectrometry
Surface Properties
Threonine
Post Translational Protein Processing
Blood Group Antigens
Serine
Mass spectrometry
Culture Media
Epitopes
Association reactions
Atoms
Antibodies
Processing

Keywords

  • Glycosylation
  • In vivo
  • Mucin
  • Tandem repeat

ASJC Scopus subject areas

  • Biochemistry

Cite this

Silverman, H. S., Parry, S., Sutton-Smith, M., Burdick, M. D., McDermott, K., Reid, C. J., ... Harris, A. (2001). In vivo glycosylation of mucin tandem repeats. Glycobiology, 11(6), 459-471.

In vivo glycosylation of mucin tandem repeats. / Silverman, Howard S.; Parry, Simon; Sutton-Smith, Mark; Burdick, Michael D.; McDermott, Kimberly; Reid, Colm J.; Batra, Surinder K.; Morris, Howard R.; Hollingsworth, Michael A.; Dell, Anne; Harris, Ann.

In: Glycobiology, Vol. 11, No. 6, 2001, p. 459-471.

Research output: Contribution to journalArticle

Silverman, HS, Parry, S, Sutton-Smith, M, Burdick, MD, McDermott, K, Reid, CJ, Batra, SK, Morris, HR, Hollingsworth, MA, Dell, A & Harris, A 2001, 'In vivo glycosylation of mucin tandem repeats', Glycobiology, vol. 11, no. 6, pp. 459-471.
Silverman HS, Parry S, Sutton-Smith M, Burdick MD, McDermott K, Reid CJ et al. In vivo glycosylation of mucin tandem repeats. Glycobiology. 2001;11(6):459-471.
Silverman, Howard S. ; Parry, Simon ; Sutton-Smith, Mark ; Burdick, Michael D. ; McDermott, Kimberly ; Reid, Colm J. ; Batra, Surinder K. ; Morris, Howard R. ; Hollingsworth, Michael A. ; Dell, Anne ; Harris, Ann. / In vivo glycosylation of mucin tandem repeats. In: Glycobiology. 2001 ; Vol. 11, No. 6. pp. 459-471.
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