Evidence for glycosylation-dependent activities of polypeptide N-acetylgalactosaminyltransferases rGalNAc-T2 and-T4 on mucin glycopeptides

• Type: Article in International Scientific Journal
• Date: 2001

Authors

Hanisch, FG (Author) Other; Celso Reis (Author) Other; Clausen, H (Author) Other; Paulsen, H (Author) Other

Journal

Title: Glycobiology

Vol. 11

Pages: 731-740

ISSN: 0959-6658

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 61 Citations

Scopus - 61 Citations

Other information

Authenticus ID: P-008-NPE

DOI: 10.1093/glycob/11.9.731

Abstract (EN): We present evidence that site-specific O-glycosylation by recombinant polypeptide N-acetylgalactosaminyltransferases rGalNAc-T2 and -T4 is controlled by the primary sequence context, as well as by the position and structure of previously introduced O-glycans. Synthetic mucin-type (glyco)peptides corresponding to sections of the tandem repeat regions of MUC1, MUC2, and MUC4 were used as substrates for recombinant polypeptide N-acetylgalactosaminyltransferases, rGalNAc-T2 and -T4. By concerted and sequential action the two transferases are able to fully glycosylate MUC1 but only partially MUC2 and MUC4 tandem repeat peptides. GalNAc residues on MUC1 acceptor peptides trigger activity of rGalNAc-T4 directed to Ser in VTSA and Thr in PDTR and of rGalNAc-T2 to Ser/Thr within the GSTA motif of variant MUC1 peptides. However, elongation of GalNAc by beta3-galactosylation inhibits rGalNAc-T4 activity completely and rGalNAc-T2 activity with respect to the acceptor site GSTA. These findings are in accord with the inhibition of rGalNAc-T2 and -T4 by fully GalNAc-substituted MUC1 repeat peptide and support a glycosylation-dependent activity induction or enhancement of both enzymes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10