N-Acetylgalactosamine-4-sulfotransferase-1 (GalNAc-4-ST1, CHST8) and N-Acetylgalactosamine-4-sulfotransferase-2 (GalNAc-4-ST2, CHST9)

Abstract

N-linked glycans terminating with the sulfate modified sequence SO ₄ -4- GalNAcβ1-4GlcNAcβ1-2Man (Fig. 102.1) were first described on bovine luteinizing hormone (LH) (Green et al. 1985). The same sequence was subsequently identified on O-linked glycans with a Core 2 structure (Fig. 102.1) that are present on pro-opiomelanocortin (POMC) (Siciliano et al. 1994). SO ₄ -4- GalNAcβ1-4GlcNAc is found on N-linked glycans of LH, thyroid stimulating hormone (TSH), and to lesser extent on follicle stimulating hormone (FSH) of all vertebrate species (Baenziger and Green 1991; Manzella et al. 1995). N-linked glycans with sulfated LacdiNAc have also been discovered on carbonic anhydrase 6 (Hooper et al. 1995a), Tamm-Horsfall glycoprotein (van Rooijen et al. 1998), tenascin-R (Woodworth et al. 2002), and SorLA/LR11 (Fiete et al. 2007). The enzymes responsible for this novel modification, CHST8 and CHST9, were cloned on the basis of their homology to HNK-1 family of sulfotransferases that includes HNK-1 sulfotransferase; chondroitin-4-sulfotransferases 1, 2, and 3; and dermatan-4-sulfotransferase 1 (Hiraoka et al. 2001; Kang et al. 2001; Okuda et al. 2000, 2003; Xia et al. 2000). CHST8 and CHST9 are able to modify LacdiNAc structures on N- and O-linked glycans in vitro and in vivo, showing little or no activity towards chondroitins or dermatan. The highest level of CHST8 expression is seen in the pituitary, consistent with its role in modifying LH, TSH, and POMC. CHST8 is also detected in various regions of the brain as well as in other tissues. CHST9 has a more limited distribution and is most prominent in the trachea.