Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII.

Abstract

L-fucose is a fundamental monosaccharide component of many mammalian glycoproteins and glycolipids. Fucosylation requires GDP-L-fucose as a donor of fucose and a specific fucosyltransferase (Fuc-T) to catalyze the transfer of L-fucose to various lactosamine acceptor molecules. The biosynthesis of GDP-L-fucose consists of two pathways. The constitutively active de novo pathway involves conversion of cellular GDP-D-mannose to GDP-L-fucose by GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (FX). In the alternative biosynthetic pathway, in the salvage metabolism, L-fucokinase (Fuk) synthesizes L-fucose-1-phosphate from free fucose. L-fucose-1-phosphate is further catalyzed to GDP-L-fucose by GDP-L-fucose pyrophosphorylase (Fpgt). GDP-L-fucose, synthesized in the cytosol, is translocated to the Golgi for fucosylation by a specific GDP-fucose transporter (FUCT1). Glycans that contain alpha(1,3)-fucosylated modifications, e.g. sialyl Lewis X-type glycans, have an important role in inflammation and in tumorigenesis. We studied the mRNA expression levels of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII by quantitative real-time PCR in mouse endothelial cells, macrophages and lymphoid tumor cells. Moreover, the expression of the same transcripts was detected in acute inflammation using rat kidney allograft as model system. Our results indicate the simultaneous upregulation of the GDP-L-fucose synthesizing enzymes of the de novo pathway, GDP-fucose transporter and fucosyltransferase VII in inflammation and in tumorigenesis.

• Authors: Jaana Niittymäki, Pirkko Mattila, Risto Renkonen
• Journal: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica (APMIS) 2006 Jul-Aug Vol. 114 Issue 7-8 Pg. 539-48 ISSN: 0903-4641 [Print] Denmark
• PMID: 16907860 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Monosaccharide Transport Proteins
• Guanosine Diphosphate Fucose
• FUT7 protein, human
• Fucosyltransferases
• fucosyltransferase VII, mouse

Topics

• Animals
• Cell Line
• Fucosyltransferases (biosynthesis, genetics)
• Gene Expression (physiology)
• Graft Rejection (metabolism)
• Guanosine Diphosphate Fucose (biosynthesis)
• Kidney Transplantation
• Mice
• Monosaccharide Transport Proteins (biosynthesis, genetics)
• Rats