Localization of UDP-GalNAc:NeuAc alpha 2,3Gal-R beta 1,4(GalNAc to Gal)N-acetylgalactosaminyltransferase in human stomach. Enzymatic synthesis of a fundic gland-specific ganglioside and GM2.

A glycolipid detected in human gastric mucosa with anti-GM2 monoclonal antibody was characterized to be GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4GlcNAc beta 1-3Gal 1-4Glc-Cer (NGM-1), which was lost in gastric cancer tissue with complementary increase of GM2 sharing the same terminal carbohydrate structure as NGM-1 (Dohi, T., Ohta, S., Hanai, N., Yamaguchi, K., and Oshima, M. (1990) J. Biol. Chem. 265, 7880-7885). The study on differential expression of NGM-1 in gastric fundic mucosa, pyloric mucosa, gastric cancer, and various other tissues indicated that NGM-1 existed specifically in fundic mucosa. The content of GM3 and sialylparagloboside (SPG), which are the substrates for the synthesis of GM2 and NGM-1, respectively, were not significantly different in these tissues. Therefore, the presence of two kinds of beta 1,4GalNAc transferases having different substrate specificity was considered to be critical for the expression of NGM-1 and GM2. The activity of beta 1,4GalNAc transferase which synthesizes GM2 or NGM-1 was determined by detecting the products with specific monoclonal antibodies. The activity of beta 1,4GalNAc transfer to SPG was high in fundic mucosa, while it was absent in pyloric mucosa or cancer. On the other hand, the increased activity of beta 1,4GalNAc transfer to GM3 was observed in cancer tissues and cancer cell lines which were rich in GM2. Our conclusion is that the limited expression of NGM-1 in fundic mucosa and the increase of GM2 in cancer are attributed to two types of beta 1,4GalNAc transferases localized in each region with different substrate specificity; the one in fundic mucosa transfers GalNAc to SPG but not to GM3, and the other one enhanced in cancer transfers GalNAc to GM3 but not to SPG.
AuthorsT Dohi, N Hanai, K Yamaguchi, M Oshima
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 266 Issue 35 Pg. 24038-43 (Dec 15 1991) ISSN: 0021-9258 [Print] UNITED STATES
PMID1748676 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Gangliosides
  • G(M2) Ganglioside
  • NGM-1
  • Galactosyltransferases
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase
  • (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
  • Antibodies, Monoclonal
  • Cell Line
  • Chromatography, Thin Layer
  • Colonic Neoplasms (enzymology)
  • G(M2) Ganglioside (analogs & derivatives, analysis, biosynthesis)
  • Galactosyltransferases (analysis, metabolism)
  • Gangliosides (analysis, biosynthesis)
  • Gastric Fundus
  • Gastric Mucosa (cytology, enzymology)
  • Humans
  • Kinetics
  • N-Acetylgalactosaminyltransferases
  • Organ Specificity
  • Pyloric Antrum
  • Stomach Neoplasms (chemistry, enzymology)

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