Expression of the developmental I antigen by a cloned human cDNA encoding a member of a beta-1,6-N-acetylglucosaminyltransferase gene family.
The blood group i/I antigens were the first identified alloantigens that display a dramatic change during human development. The i and I antigens are determined by linear and branched poly-N-acetyllactosaminoglycans, respectively. In human erythrocytes during embryonic development, the fetal (i) antigen is replaced by the adult (I) antigen as a result of the appearance of a beta-1,6-N-acetylglucosaminyltransferase, the I-branching enzyme. Here, we report the cDNA cloning and expression of this branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans, thus introducing the I antigen in transfected cells. The cDNA sequence predicts a protein with type II membrane topology as has been found for all other mammalian glycosyltransferases cloned to date. The Chinese hamster ovary cells that stably express the isolated cDNA acquire I-branched structures as evidenced by the structural analysis of glycopeptides from these cells. Comparison of the amino acid sequence with those of other glycosyltransferases revealed that this I-branching enzyme and another beta-1,6-N-acetylglucosaminyltransferase that forms a branch in O-glycans are strongly homologous in the center of their putative catalytic domains. Moreover, the genes encoding these two beta-1,6-N-acetylglucosaminyltransferases were found to be located at the same locus on chromosome 9, band q21. These results indicate that the I-branching enzyme represents a member of a beta-1,6-N-acetylglucosaminyltransferase gene family of which expression is controlled by developmental programs.
Bierhuizen
M F
MF
La Jolla Cancer Research Foundation, Cancer Research Center, California 92037.
Mattei
M G
MG
Fukuda
M
M
D000328:Adult; D000818:Animals; D016466:CHO Cells; D002240:Carbohydrate Sequence; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular / Q000379:methods; D006224:Cricetinae; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D004912:Erythrocytes / Q000201:enzymology; D006020:Glycopeptides / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D007048:I Blood-Group System / Q000235:genetics*; D007519:Isoantigens / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D006020:Glycopeptides; D007048:I Blood-Group System; D007519:Isoantigens; D004247:DNA; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase