Glycosyltransferases: cell surface remodeling and regulation of receptor tyrosine kinases-induced signaling*

The biosynthesis and degradation of glycoconjugates are catalyzed by glycosyltransferases and glycosidases, respectively, and the genes which encode glycosyltransferases and related proteins are referred to as `glyco-genes'. The expression of glycosyltransferases, the substrate speci®city of the enzymes and their subcellular localization represent key determinants in the biosynthesis of sugar chain [1±6]. In recent years several glycosyltransferases have been identi®ed, cloned and characterized. However, the biological signi®cance of these genes and their precise physiological function still remain elusive. One of the strategies used in the elucidation of the physiological function of glycosyltransferases is to manipulate the expression levels of glyco-genes in mammalian cells. Even though a speci®c glycosyltransferase gene is over-expressed or knocked out in mammalian cells, due to the abundance of glycoconjugates, the resulting phenotypic changes are rather complex [4] because those changes are due to a direct effect of glycosyltransferase gene or an indirect one. It is essential to identify the likely target glycoconjugates under those conditions. It is noteworthy that the recent manipulation of glyco-genes in animal models in our and several other laboratories have opened new insights in the area of glycobiology or glycotechnology in terms of phenotypic changes of cells and tissues.