2 NATURALLY-OCCURRING ALPHA-2,6-SIALYLTRANSFERASE FORMS WITH A SINGLEAMINO-ACID CHANGE IN THE CATALYTIC DOMAIN DIFFER IN THEIR CATALYTIC ACTIVITY AND PROTEOLYTIC PROCESSING

The alpha 2,6-sialyltransferase (ST) is a Golgi glycosyltransferase th at adds sialic acid residues to glycoprotein N-linked oligosaccharides . Here we show that two forms of alpha 2,6-sialyltransferase are expre ssed by the liver and are encoded by two different RNAs that differ by a single nucleotide, The ST tyr possesses a Tyr at amino acid 123, wh ereas the ST cys possesses a Cys at this position. The ST tyr is more catalytically active than the ST cys; however, both are functional whe n introduced into tissue culture cells, The proteolytic processing and turnover of the ST tyr and ST cys proteins differ dramatically, The S T cys is retained intact in COS-1 cells, whereas the ST tyr is rapidly cleaved and secreted, Analysis of the N-linked oligosaccharides of th ese proteins demonstrates that both proteins enter the late Golgi. How ever, differences in ST tyr and ST cys proteolytic processing may be r elated to differences in their localization, because ST tyr but not ST cys is expressed at low levels on the cell surface, The possibility t hat the ST tyr is cleaved in a post-Golgi compartment is supported by the observation that a 20 degrees C temperature block, which stops pro tein transport in the trans Golgi network, blocks both cleavage and se cretion of the ST tyr.