Hiraoka N, Misra A, Belot F, Hindsgaul O, Fukuda M
Glycobiology Program, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA.
Glycobiology. 2001 Jun;11(6):495-504. doi: 10.1093/glycob/11.6.495.
Recently, cDNAs encoding human chondroitin 4-O-sulfotransferase-1 and -2 (C4ST-1 and C4ST-2) were cloned based on their similarity to HNK-1 sulfotransferase (HNK-1ST) (Hiraoka, N., Nakagawa, H., Ong, E., Akama, T.O., Fukuda, M.N., and Fukuda, M. [2000] Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family. J. Biol. Chem., 275, 20188--20196). In the present study, we identified two additional novel sulfotransferases by searching the expression sequence tag and genomic DNA database for enzymes similar to C4ST-1 and C4ST-2. These newly cloned enzymes, termed GalNAc4ST-1 and GalNAc4ST-2, belong to the HNK-1ST gene family having 40--42% identity with C4ST-1. GalNAc4ST-1 and -2 do not add sulfate to HNK-1 precursor glycans, chondroitin, or desulfated dermatan sulfate. Instead, both enzymes can transfer sulfate to the 4-position of GalNAc in the context of GalNAc beta 1-->4GlcNAc beta 1-->R attached to both N-linked and core 2 branched O-linked oligosaccharides. GalNAc4ST-1 and -2 transcripts are highly expressed in the pituitary gland and trachea, respectively, and GalNAc4ST-1 and -2 transcripts are reciprocally expressed in other tissues as well. Moreover, both enzymes can transfer sulfate to lutropin, a pituitary glycoprotein hormone. These combined results indicate that GalNAc4ST-1 and -2 play critical roles in forming sulfo-->4GalNAc beta 1-->4GlcNAc beta 1-->R in both N-glycans and O-glycans in a tissue-specific manner.
最近，基于与HNK-1硫酸转移酶（HNK-1ST）的相似性，编码人软骨素4-O-硫酸转移酶-1和-2（C4ST-1和C4ST-2）的cDNA被克隆出来（平冈，N.，中川，H.，翁，E.，赤间，T.O.，福田，M.N.，以及福田，M. [2000] 属于HNK-1硫酸转移酶基因家族的两种不同的人软骨素4-O-硫酸转移酶的分子克隆及表达。《生物化学杂志》，275，20188 - 20196）。在本研究中，我们通过在表达序列标签和基因组DNA数据库中搜索与C4ST-1和C4ST-2相似的酶，鉴定出另外两种新型硫酸转移酶。这些新克隆的酶，称为GalNAc4ST-1和GalNAc4ST-2，属于HNK-1ST基因家族，与C4ST-1具有40 - 42%的同一性。GalNAc4ST-1和-2不会将硫酸盐添加到HNK-1前体聚糖、软骨素或去硫酸化的硫酸皮肤素上。相反，这两种酶都可以在连接到N-连接和核心2分支O-连接寡糖上的GalNAcβ1→4GlcNAcβ1→R的背景下，将硫酸盐转移到GalNAc的4位。GalNAc4ST-1和-2转录本分别在垂体和气管中高表达，并且GalNAc4ST-1和-2转录本在其他组织中也呈相互表达。此外，这两种酶都可以将硫酸盐转移到促黄体激素（一种垂体糖蛋白激素）上。这些综合结果表明，GalNAc4ST-1和-2在以组织特异性方式在N-聚糖和O-聚糖中形成磺基→4GalNAcβ1→4GlcNAcβ1→R方面发挥关键作用。
