Sulf2

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Sulf-2 exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Heparan sulfate proteoglycans act as co-receptors for numerous heparin-_x000b_binding growth factors and cytokines and are key regulators of_x000b_cell signaling. Growth factor binding to heparan sulfate results in mitogenic activity only when specific structural features are present within the heparan sulfate chains. These features include sulfation at specific positions within a disaccharide (N, 2-O, 3-O, 6-O) by the enzymes that regulate heparan sulfate synthesis inside the Golgi. Following synthesis and expression, heparan sulfate can be structurally and functionally modified within the extracellular compartment. Enzymes known to have these effects are heparanase, which cleaves heparan sulfate chains into smaller biologically active fragments, and the heparan sulfate 6-O-endosulfatases (Sulfs). The Sulfs represent a new and novel family of enzymes that are secreted via the Golgi and subsequently localized to the cell surface or may be released into the extracellular matrix. Sulf-1 enzyme is required for Wnt-mediated signaling in developing quail muscle. Sulf1 was shown (in quial) to restore bone morphogenetic protein_x000b_signaling in cells by releasing the functional inhibitor, Noggin, from cell_x000b_surfaces. Quail Sulf1 can also inhibit growth factor signaling,_x000b_the removal of the 6-O-sulfation is required for the formation of the_x000b_FGF HS FR1c ternary complex blocking FGF2 signaling. Analysis of human tumor tissue and tumor cell lines suggests that_x000b_HSulf-1 is misregulated in cancers. HSulf-1 is found in a variety of_x000b_normal tissues but is down-regulated in tumor cell lines originating_x000b_from ovarian, breast, pancreatic, renal, and hepatocellular carcinoma. Tumors formed by cells expressing Sulf demonstrate enhanced extracellular matrix deposition. The 6-O-sulfation of heparan sulfate of myeloma tumor cells may be a critical factor in determiningand regulating the in vivo growth of this cancer. Synonyms: Extracellular Sulfatase-2, HSulf-2 <