EXPRESSION CLONING OF FORSSMAN GLYCOLIPID SYNTHETASE - A NOVEL MEMBEROF THE HISTO-BLOOD GROUP ABO GENE FAMILY

A phenotypic cloning approach was used to isolate a canine cDNA encodi ng Forssman glycolipid synthetase (FS; UDP-GalNAc:globoside alpha-1,3- N-acetylgalactosaminyltransferase; EC 2.4.1.88), The deduced amino aci d sequence of FS demonstrates extensive identity to three previously c loned glycosyltransferases, including the enzymes responsible for synt hesis of histo-blood group A and B antigens, These three enzymes, like FS, catalyze the addition of either N-acetylgalactosamine (GalNAc) or galactose (Gal) in alpha-1,3-linkage to their respective substrates, Despite the high degree of sequence similarity among the transferases, we demonstrate that the FS cDNA encodes an enzyme capable of synthesi zing Forssman glycolipid, and demonstrates no GalNAc or Gal transferas e activity when closely related substrates are examined, Thus, the FS cDNA is a novel member of the histo-blood group ABO gene family that e ncodes glycosyltransferases with related but distinct substrate specif icity, Cloning of the FS cDNA will allow a detailed dissection of the roles Forssman glycolipid plays in cellular differentiation, developme nt, and malignant transformation.