Alpha-1,4-NAcetylglucosaminyltransferase (A4GNT)

Abstract

α1,4-N-acetylglucosaminyltransferase (α4GnT) is a glycosyltransferase that mediates transfer of GlcNAc from UDP-GlcNAc to βGal residues with α1,4-linkage preferentially present in O-glycans forming GlcNAcα1→4Galβ→R, and cDNA encoding α4GnT was isolated from a human stomach cDNA library by expression cloning. In normal human tissues, O-glycans exhibiting GlcNAcα1→4Galβ→R at nonreducing terminal (αGlcNAc) are exclusively limited to gland mucin secreted from gland mucous cells of the stomach and Brunner’s gland of the duodenum. αGlcNAc in gland mucin is detected by immunohistochemistry with HIK1083 antibody and paradoxical ConA staining. Notably, αGlcNAc inhibits the growth and motility of Helicobacter pylori (H. pylori) by inhibiting the biosynthesis of its cell wall component cholesteryl-α-D-glucopyranoside. In addition, A4gnt-/- mice show no αGlcNAc in gland mucin in the gastroduodenal mucosa, and develop gastric differentiated-type adenocarcinoma through inflammation-associated pathways, even in the absence of H. pylori infection. Thus, αGlcNAc in gland mucin plays a dual role in protecting gland mucous cells from H. pylori infection and also serving as a tumor suppressor of differentiated-type gastric adenocarcinoma.