Heparan-sulfate 6-O-sulfotransferase 1-3 (HS6ST1-3)

Abstract

The functions of heparan sulfate (HS) are involved in various cellular processes such as proliferation, differentiation, adhesion, migration, morphology, and maintenance of stem cells (Habuchi et al. 2004; Bishop et al. 2007; Lindahl and Li 2009; Buresh et al. 2010; Shah et al. 2011; Buresh-Stiemke et al. 2012). It has been shown that HS plays some roles in various physiological phenomena such as inflammation, blood coagulation, tumor cell invasion, and malignancy. Moreover, infections of host cells with pathogens such as viruses, bacteria, and parasites have been shown to occur through the interactions with cell surface HS on host cells (Mettenleiter et al. 1990; Trybala et al. 1996; Liu and Thorp 2002). 6-O-Sulfate residues in HS are greatly involved in the above various biological and pathological processes primarily by modulating various signal transduction pathways such as fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), Wnts, and hedgehog. HS 6-O-sulfotransferases (HS6STs) transfer sulfate to position 6 of the N-sulfoglucosamine/N-acetylglucosamine residue in heparin/HS. Three isoforms are identified in mouse and human. All HS6STs are type II transmembrane proteins with short cytoplasmic domain at the N-terminus, followed by transmembrane and luminal domain which have 3′-phosphoadenosine 5′- phosphosulfate (PAPS) binding site and sulfotransferase activity localized at the Golgi apparatus.