Abstract
The UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T3, exhibits unique functions. Specific acceptor substrates are used by GalNAc-T3 and not by other GalNAc-transferases. The expression pattern of GalNAc-T3 is restricted, and loss of expression is a characteristic feature of poorly differentiated pancreatic tumors. In the present study, a sixth human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T6, with high similarity to GalNAc-T3, was characterized. GalNAc-T6 exhibited high sequence similarity to GalNAc-T3 throughout the coding region, in contrast to the limited similarity that exists between homologous glycosyltransferase genes, which is usually restricted to the putative catalytic domain. The genomic organizations of GALNT3 and GALNT6 are identical with the coding regions placed in 10 exons, but the genes are localized differently at 2q31 and 12q13, respectively. Acceptor substrate specificities of GalNAc-T3 and -T6 were similar and different from other GalNAc-transferases. Northern analysis revealed distinct expression patterns, which were confirmed by immunocytology using monoclonal antibodies. In contrast to GalNAc-T3, GalNAc-T6 was expressed in WI38 fibroblast cells, indicating that GalNAc-T6 represents a candidate for synthesis of oncofetal fibronectin. The results demonstrate the existence of genetic redundancy of a polypeptide GalNAc-transferase that does not provide full functional redundancy.
Highlights
The UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T3, exhibits unique functions
In contrast to GalNAc-T3, GalNAc-T6 was expressed in WI38 fibroblast cells, indicating that GalNAc-T6 represents a candidate for synthesis of oncofetal fibronectin
Recent studies with a panel of monoclonal antibodies to human GalNAc-transferases demonstrated that GalNAc-T3 is not expressed in connective tissue cells in normal or tumor tissues or in a fibroblast cell line synthesizing oncofetal fibronectin [16]
Summary
Eric Paul Bennett‡, Helle Hassan‡, Ulla Mandel‡, Michael A. The catalytic action of the different GalNAc-transferases can be cooperative, since glycosylation of certain acceptor sites in the MUC1 tandem repeat by one GalNAc-transferase is required before other sites can be glycosylated by another GalNActransferase [6] These data suggest that each GalNAc-transferase has distinct biological functions that are mainly determined by the kinetic properties and expression patterns of the enzymes. It is unlikely that GalNAc-T3 represents the native fibronectin GalNAc-transferase activity found in tumor tissues and fibroblast cell lines, as originally described by Matsuura et al [17] This suggests the existence of an additional GalNActransferase with similar properties as GalNAc-T3 but with a different expression pattern. The existence of high similarity pairs of genes within the GalNAc-transferase gene family is significant to the biological function of this large gene family and of practical significance for studies of transgenic knock-out models
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